- Optical resolution, characterization, and X-ray crystal structures of diastereomeric salts of chiral amino acids with (S)-(-)-1-phenylethanesulfonic acid
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Ten DL-Amino acids (AA), including neutral, and basic amino acids, and an imino acid, were optically resolved, without derivatization into their covalent compounds, by means of fractional crystallization of their diastereomeric salts with (-)-1-phenylethanesulfonic acid (PES) in various solvents. Several pairs of the diastereomeric crystalline salts formed during the resolutions were analyzed by DSC and spectroscopy, which showed that the successful resolutions were attributable to differences in various physicochemical properties between the more-soluble D-AA · (-)-PES and less-soluble L-AA · (-)-PES. Chiral recognition of the most successfully resolved species, DL-p-hydroxyphenylglycine (HPG) salt, was explored by comparing the X-ray crystal structures of D- and L-HPG · (-)-PES. The two crystal structures differed obviously in their hydrogen-bonding networks: the less-soluble L-HPG · (-)-PES only had strong hydrogen-bonded infinite chains of HPG in a 'head-to-tail' arrangement through the p-hydroxyl group, the structure of which was more geometrically stable than that of the more-soluble D-HPG · (-)-PES. The differences in the two crystal structures related to striking differences in their solubilities and thermal properties.
- Yoshioka,Ohtsuki,Da-Te,Okamura,Senuma
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- Tasiamide F, a potent inhibitor of cathepsins D and E from a marine cyanobacterium
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In search of novel protease inhibitors with therapeutic potential, our efforts exploring the marine cyanobacterium Lyngbya sp. have led to the discovery of tasiamide F (1), which is an analogue of tasiamide B (2). The structure was elucidated using a combination of NMR spectroscopy and mass spectrometry. The key structural feature in 1 is the presence of the Phe-derived statine core, which contributes to its aspartic protease inhibitory activity. The antiproteolytic activity of 1 and 2 was evaluated in vitro against cathepsins D and E, and BACE1. Tasiamide F (1) displayed IC50values of 57?nM, 23?nM, and 0.69?μM, respectively, indicating greater selectivity for cathepsins over BACE1 compared with tasiamide B (2). Molecular docking experiments were carried out for compounds 1 and 2 against cathepsins D and E to rationalize their activity towards these proteases. The dysregulated activities of cathepsins D and E have been implicated in cancer and modulation of immune responses, respectively, and these proteases represent potential therapeutic targets.
- Al-Awadhi, Fatma H.,Ratnayake, Ranjala,Paul, Valerie J.,Luesch, Hendrik
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- The relative catalytic efficiency of β-lactamase catalyzed acyl and phosphyl transfer
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Phosphonamidates which bear a simple resemblance to penicillin type structures have been synthesised as potential inhibitors of β-lactamases: -ethyl N-(benzyloxycarbonyl) amidomethyl phosphonyl amides, PhCH2OCONHCH2P(O)(OEt)NR2, the amines HNR2 being L-proline, D-proline, L-thiazolidine, and o-anthranilic acid. The proline derivatives completely and irreversibly inactivated the class C β-lactamase from Enterobacter cloacae P99, in a time-dependent manner, indicative of covalent inhibition. The inactivation was found to be exclusive to the class C enzyme and no significant inhibition was observed with any other class of β-lactamase. The anthranilic acid derivative exhibited no appreciable inactivation of the β-lactamases. The phosphonyl proline and phosphonyl thioproline derivatives were separated into their diastereoisomers and their individual second order rate constants for inhibition were found to be 7.72 ± 0.37 and 8.3 × 10-2 ± 0.004 M-1 s-1 for the L-proline derivatives, at pH 7.0. The products of the inhibition reaction of each individual diastereoisomer, analyzed by electrospray mass spectroscopy, indicate that the more reactive diastereoisomers phosphonylate the enzyme by P-N bond fission with the elimination of proline. Conversely, gas chromatographic detection of ethanol release by the less reactive proline diastereoisomer suggests phosphonylation occurs by P-O bond fission. The enzyme enhances the rate of phosphonylation with P-N fission by at least 106 compared with that effected by hydroxide-ion. The pH dependence of the rate of inhibition of the β-lactamase by the more reactive diasteroisomer is consistent with the reaction of the diprotonated form of the enzyme, EH2, with the inhibitor, I (or its kinetic equivalents EH with IH). This pH dependence and the rate enhancement indicate that the enzyme appears to use the same catalytic apparatus for phosphonylation as that used for hydrolysis of β-lactams. The stereochemical consequences of nucleophilic displacement at the phosphonyl centre are discussed.
- Slater, Martin J.,Laws, Andrew P.,Page, Michael I.
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- Cyclopentapeptides from Dianthus chinensis
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A new cyclopentapeptide dianthin I (1), together with two known ones pseudostellarin A (2) and heterophyllin J (3), was isolated from the aerial parts of Dianthus chinensis. The structure of 1 was elucidated as cyclo-(Gly1- l-Phe2- l-Pro3- l-Ser4- l-Phe5) on the basis of extensive spectroscopic analyses and chemical methods.
- Han, Jing,Huang, Maobo,Wang, Zhe,Zheng, Yuqing,Zeng, Guangzhi,He, Wenjun,Tan, Ninghua
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- Viridamides A and B, lipodepsipeptides with antiprotozoal activity from the marine cyanobacterium Oscillatoria nigro-viridis
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Parallel chemical and phylogenetic investigation of a marine cyanobacterium from Panama led to the isolation of two new PKS-NRPS-derived compounds, viridamides A and B. Their structures were determined by NMR and mass spectroscopic methods, and the absolute configurations assigned by Marfey's method and chiral HPLC analysis. In addition to six standard, N-methylated amino and hydroxy acids, these metabolites contained the structurally novel 5-methoxydec-9-ynoic acid moiety and an unusual proline methyl ester terminus. Morphologically, this cyanobacterium was identified as Oscillatoria nigro-viridis, and its 16S rDNA sequence is reported here for the first time. Phylogenetic analysis of these sequence data has identified O. nigro-viridis strain OSC3L to be closely related to two other marine cyanobacterial genera, Trichodesmium and Blennothrix. Viridamide A showed antitrypanosomal activity with an IC50 of 1.1 μM and antileishmanial activity with an IC50 of 1.5 μM.
- Simmons, T. Luke,Engene, Niclas,Urena, Luis David,Romero, Luz I.,Ortega-Barria, Eduardo,Gerwick, Lena,Gerwick, William H.
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- Structure of the Antifungal Nucleotide Antibiotic Phosmidosine
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The structure of phosmidosine (1), a novel proline-containing nucleotide antibiotic from Streptomyces durhameusis, active against the pathogenic fungus Botrytis cinerea, was determined by mass spectrometry and NMR spectroscopy.Homologs 2, 3, and the isomer 4 were detected and characterized using approaches based principally on tandem mass spectrometry and combined liquid chromatography-mass spectrometry which permitted assignment of most structural features directly in the crude isolate without prior isolation of individual components.Conversion of 1-4 to the O-isopropylidene derivatives 1a-4a by a microscale procedure resulted in enhanced fast atom bombardment ionization (FAB) signal to background sensitivity.Collision-induced dissociation mass spectra were aquired from molecular ions and ion source-generated fragment ions and used in conjunction with FAB-deuterium exchange methods for the assignment of structural differences between 1a-4a.
- Phillips, Dennis R.,Uramoto, Masakazu,Isono, Kiyoshi,McCloskey, James A.
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- Structures and solution conformational dynamics of stylissamides G and H from the Bahamian Sponge Stylissa caribica
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Two new peptides, stylissamides G and H, were isolated from extracts of a sample of Stylissa caribica collected in deep waters of the Caribbean Sea. A single sample of S. caribica among a collection of 10 samples that were examined by LC-MS appeared to be a different chemotype from the others in that it lacked the familiar pyrrole-2-aminoimidazole alkaloids, stevensine and oroidin, and contained peptides of the stylissamide class. The structures of the title compounds were solved by integrated analysis of the MS and NMR spectra and chemical degradation. The solution conformation of stylissamide G was briefly examined by electronic circular dichroism and temperature-dependent 1H NMR chemical shifts of amide NH signals, which supported a conformationally rigid macrocycle.
- Wang, Xiao,Morinaka, Brandon I.,Molinski, Tadeusz F.
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- Kinetics and mechanism of oxidation of captopril by diperiodatocuprate(III) in aqueous alkaline medium
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Captopril is a sulfur containing drug which inhibits angiotensin-converting enzyme. Its kinetics of oxidation were studied spectrophotometrically using diperiodatocuprate(III) in aqueous alkali. Major oxidative product of captopril was identified as captopril disulfide along with trace amount of the hydrolyzed product, l-proline. Kinetics of oxidation was found to be first order each in [oxidant] and [reductant]. Rate of reaction was decreased by increasing [OH-], whereas added periodate retarded the rate. Other kinetic parameters viz., ionic strength, dielectric constant, temperature effect, and intervention of free radical were also studied. Activation parameters like EA, ΔH#, ΔS#, ΔG #, and log A were calculated. A suitable mechanism was proposed. Rate law for proposed mechanism was derived and verified. Reaction constants involved in various steps of mechanism were evaluated and used to regenerate first-order experimental rate constants at various experimental conditions.
- Angadi, Mahantesh A.,Tuwar, Suresh M.
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- Heterogeneous Asymmetric Hydrogenation of a Chiral Tripeptide containing Dehydroalanine and α,β-Dehydrobutyrine Residues
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The heterogeneous asymmetric hydrogenation of a linear tripeptide containing dehydroalanine and α,β-dehydrobutyrine has been carried out, giving asymmetric yields of alanine and butyrine of 94 and 54percent, respectively.
- Takasaki, Michiaki,Harada, Kaoru
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- Enantioselective Enzymatic Cleavage of N-Benzyloxycarbonyl Groups
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A new enzymatic process for the enantioselective cleavage of N-benzyloxycarbonyl (Cbz) groups from protected amino acids and related compounds has been developed. The Cbz-deprotecting enzyme was isolated from cell extracts of Sphingomonas paucimobilis SC 16113 and purified to homogeneity. The purified protein has a molecular weight of 155,000 daltons and a subunit size of 44,000 daltons.
- Patel, Ramesh N.,Nanduri, Venkata,Brzozowski, David,McNamee, Clyde,Banerjee, Amit
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- New diketopiperazine derivatives isolated from sea urchin-derived Bacillus sp.
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Two new diketopiperazine derivatives, bacillusamides A (1) and B (2), have been isolated from the EtOAc extract of the sea urchin-derived Bacillus sp. along with the known cyclo(-L-pro-L-val-) (3), cyclo(-L-pro-L-tyr-) (4), cyclo(-L-pro-L-phe-) (5). These structures were elucidated by extensive spectroscopic methods. Furthermore, the absolute configurations of the amino acid residues were determined using Marfey's method. Compound 1 displayed weak antifungal activity against Aspergillus niger.
- Yonezawa, Ken,Yamada, Koji,Kouno, Isao
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- Efficient deprotection of N-benzyloxycarbonyl group from amino acids by hydroxyapatite-bound Pd catalyst in the presence of molecular hydrogen
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Hydroxyapatite-bound Pd catalyst was found to be highly effective for the deprotection of N-benzyloxycarbonyl group from amino acids in the presence of molecular hydrogen. The catalyst was also applicable to the hydrogenolysis of a sterically encumbered core-Z-protected poly(amido amine) dendrimer, affording the dendritic amino compound in 99% yield.
- Murata, Makoto,Hara, Takayoshi,Mori, Kohsuke,Ooe, Masahiko,Mizugaki, Tomoo,Ebitani, Kohki,Kaneda, Kiyotomi
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- Cipralphelin, a new anti-oxidative N-cinnamoyl tripeptide produced by the deep sea-derived fungal strain Penicillium brevicompactum FKJ-0123
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A new N-cinnamoyl tripeptide, designated cipralphelin (1), was isolated from a cultured broth of Penicillium brevicompactum FKJ-0123 by physicochemical (PC) screening. Compound 1 was purified by silica gel and ODS column chromatography followed by preparative HPLC. The structure of 1 was determined as N-cinnamoyl-prolyl-alanyl-phenylalanine methyl ester by nuclear magnetic resonance and mass spectrometry analyses. The absolute configurations of three amino acids were determined by an advanced Marfey’s method applied to the hydrolysate of 1. Compound 1 was evaluated for its cytotoxicity, anti-microbial activity, and ability to scavenge or quench reactive oxygen species (ROS) such as superoxide anion radicals, hydroxy radicals, and singlet oxygen. Compound 1 exhibited potent scavenging activity against hydroxy radicals.
- Matsuo, Hirotaka,Mokudai, Takayuki,Higo, Mayuka,Nonaka, Kenichi,Nagano, Yuriko,Nagahama, Takahiko,Niwano, Yoshimi,Takahashi, Yōko,ōmura, Satoshi,Nakashima, Takuji
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- An improved and practical approach to essentially enantiopure BINOLs: Enantioselective inclusion complexation of (S)-proline
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An improved and practical approach to (R)- and (S)-BINOLs has been developed. The rac-BINOL and (S)-proline were refluxed in acetonitrile for several hours, and the resulting white precipitate was recrystallized in ethanol to afford colorless crystals con
- Hu, Xiaoyun,Chang, Qing,Shan, Zixing
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- Dudawalamides A-D, Antiparasitic Cyclic Depsipeptides from the Marine Cyanobacterium Moorea producens
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A family of 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya)-containing cyclic depsipeptides, named dudawalamides A-D (1-4), was isolated from a Papua New Guinean field collection of the cyanobacterium Moorea producens using bioassay-guided and spectroscopic approaches. The planar structures of dudawalamides A-D were determined by a combination of 1D and 2D NMR experiments and MS analysis, whereas the absolute configurations were determined by X-ray crystallography, modified Marfey's analysis, chiral-phase GCMS, and chiral-phase HPLC. Dudawalamides A-D possess a broad spectrum of antiparasitic activity with minimal mammalian cell cytotoxicity. Comparative analysis of the Dhoya-containing class of lipopeptides reveals intriguing structure-activity relationship features of these NRPS-PKS-derived metabolites and their derivatives.
- Almaliti, Jehad,Malloy, Karla L.,Glukhov, Evgenia,Spadafora, Carmenza,Gutiérrez, Marcelino,Gerwick, William H.
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- Synergie effect of two metal centers in catalytic hydrolysis of methionine-containing peptides promoted by dinuclear palladium(II) hexaazacyclooctadecane complex
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The species obtained by the reaction of [Pd2([18]aneN 6)Cl2](ClO4)2 (where [18]aneN 6 is 1,4,7,10,13,16-hexaazacyclooctadecane) with AgBF4 have been determined by electrospray ionization mass spectrometry (ESI-MS) to be an equilibrium mixture of three major types of dinuclear Pd(II) complex cations, [Pd2(-O)([18]aneN6)]2+, [Pd 2(μ-OH)-([18]aneN6)]3+ and [Pd 2(H2O)(OH)([18]aneN6)]3+, in aqueous solution. The hydroxo-group-bridged one, [Pd2(μ-OH)-([18] aneN6)]3+, is a dominant species, whose crystal structure has been obtained. The crystal structure of [Pd2(μ-OH)-([18] aneN6)](ClO4)3 shows that each Pd(II) ion in the dinuclear complex is tetra-coordinated by three nitrogen atoms and one hydroxo group bridge in a distorted square configuration. The two Pd(II) ions are 3.09 A apart from each other. The dinuclear Pd(II) complex cations [Pd2(μ-OH)([18]aneN6)]3+ and [Pd 2(H2O)(OH)([18]aneN6)]3+ can efficiently catalyze hydrolysis of the amide bond involving the carbonyl group of methionine in methionine-containing peptides with turnover number of larger than 20. In these hydrolytic reactions, the two Pd(II) ions are synergic; one Pd(II) ion anchors to the side chain of methionine and the other one delivers hydroxo group or aqua ligand to carbonyl carbon of methionine, or acts as a Lewis acid to activate the carbonyl group of methionine, resulting in cleavage of Met-X bond. The binding constant of dinuclear Pd(II) complex cations with AcMet-Gly and AcMet were determined by 1H NMR titration to be 282±2 M-1 and 366±4 M-1, respectively. The relatively low binding constants enable the catalytic cycle and the possible catalytic mechanism is proposed. This is the first artificial mimic of metallopeptidases with two metal active centers. The Royal Society of Chemistry 2005.
- Yang, Gaosheng,Miao, Ren,Li, Yizhi,Hong, Jing,Zhao, Chuenmei,Guo, Zijian,Zhu, Longgen
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- Unique polyhalogenated peptides from the marine sponge Ircinia sp.
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Two new bromopyrrole peptides, haloirciniamide A (1) and seribunamide A (2), have been isolated from an Indonesian marine sponge of the genus Ircinia collected in the Thousand Islands (Indonesia). The planar structure of both compounds was assigned on the basis of extensive 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configuration of the amino acid residues in 1 and 2 was determined by the application of Marfey's method. Compound 1 is the first dibromopyrrole cyclopeptide having a chlorohistidine ring, while compound 2 is a rare peptide possessing a tribromopyrrole ring. Both compounds failed to show significant cytotoxicity against four human tumor cell lines, and neither compound was able to inhibit the enzyme topoisomerase I or impair the interaction between programmed cell death protein PD1 and its ligand, PDL1.
- Fernández, Rogelio,Bayu, Asep,Hadi, Tri Aryono,Bueno, Santiago,Pérez, Marta,Cuevas, Carmen,Putra, Masteria Yunovilsa
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- Isolation and synthesis of falcitidin, a novel myxobacterial-derived acyltetrapeptide with activity against the malaria target falcipain-2
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A 384-well microtitre plate fluorescence cleavage assay was developed to identify inhibitors of the cysteine protease falcipain-2, an important antimalarial drug target. Bioassay-guided isolation of a MeOH extract from a myxobacterium Chitinophaga sp. Y23 isolated from soil collected in Singapore, led to the identification of a new acyltetrapeptide, falcitidin (1), which displayed an IC 50 value of 6 μM against falcipain-2. The planar structure of 1 was secured by NMR and MS/MS analysis. Attempts to isolate further material for biological testing were hampered by inconsistent production and by a low yield (100 μg l -1). The absolute configuration of 1 was determined by Marfey's analysis and the structure was confirmed through total synthesis as isovaleric acid-D-His-L-Ile-L-Val-L-Pro-NH 2. Falcitidin (1) is the first member of a new class of falcipain-2 inhibitors and, unlike other peptide-based inhibitors, does not contain reactive groups that irreversibly bind to active cysteine sites.
- Somanadhan, Brinda,Kotturi, Santosh R.,Yan Leong, Chung,Glover, Robert P.,Huang, Yicun,Flotow, Horst,Buss, Antony D.,Lear, Martin J.,Butler, Mark S.
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- Mutation in the substrate-binding site of aminopeptidase B confers new enzymatic properties
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Aminopeptidase B (Ap-B) catalyzes the cleavage of arginine and lysine residues at the N-terminus of various peptide substrates. In vivo, it participates notably in the miniglucagon and cholecystokinin 8 processing, but the complete range of physiological functions of Ap-B remains to be discovered. Ap-B is a member of the M1 family of Zn2+-metallopeptidases that are characterized by two highly conserved motives, GXMEN (potential substrate binding site) and HEXXHX18E (Zn2+-binding site). In this study, mutagenesis and molecular modelling were used to investigate the enzymatic mechanism of Ap-B. Nineteen rat Ap-B mutants of the G 298XM300E301N302 motif and one mutant of the HEIS328HX18E motif were expressed in Escherichia coli. All mutations except G298P, G298S, and S328A abolished the aminopeptidase activity. The S328A mutant mimics the sequence of bovine Ap-B Zn2+-binding site, which differs from those of other mammalian Ap-B. This mutant conserved a canonical Ap-B activity. G298S and G298P mutants exhibit new enzymatic properties such as changes in their profile of inhibition and their sensitivity to Cl- anions. Moreover, the G298P mutant exhibits new substrate specificity. A structural analysis using circular dichroism, fluorescence spectroscopy, molecular modelling and dynamics was performed to investigate the role that residue G298 plays in the catalytic mechanism of Ap-B. Our results show that G298 is essential to Ap-B activity and participates to the substrate specificity of the enzyme.
- Pham, Viet-La?,Gouzy-Darmon, Cécile,Pernier, Julien,Hanquez, Chantal,Hook, Vivian,Beinfeld, Margery C.,Nicolas, Pierre,Etchebest, Catherine,Foulon, Thierry,Cadel, Sandrine
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- Tunicyclin a, the first plant tricyclic ring cycloheptapeptide from Psammosilene tunicoides
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A novel cycloheptapeptide, tunicyclin A, with a unique tricyclic ring cyclopeptide skeleton, was isolated from Psammosilene tunicoides. Its structure was elucidated by extensive NMR and MS analysis. Biogenetically, tunicyclin A might be derived from cyclo
- Tian, Jun-Mian,Shen, Yun-Heng,Yang, Xian-Wen,Liang, Shuang,Tang, Jian,Shan, Lei,Zhang, Wei-Dong
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- Komesuamide and odopenicillatamide, two linear lipopeptides from the marine cyanobacterium Caldora penicillata
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The linear lipopeptides komesuamide (1) and odopenicillatamide (2) were isolated from Caldora penicillata a marine cyanobacterium collected in Okinawa. The structures of these compounds were established by spectroscopic analyses, and the absolute configurations were determined by HPLC analyses of the acid hydrolysates. Both compounds showed glucose uptake activity at 40 μM in cultured L6 myotubes.
- Ozaki, Kaori,Jinno, Atsuhide,Natsume, Noriyuki,Sumimoto, Shimpei,Iwasaki, Arihiro,Suenaga, Kiyotake,Teruya, Toshiaki
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- Specialized metabolites from the aerial parts of Centaurea polyclada DC.
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The genus Centaurea L. (Asteraceae) is represented by 200 taxa in the flora of Turkey and several Centaurea species are used as herbal remedies against different conditions. Previous phytochemical investigations on this genus generally revealed the isolation of sesquiterpene lactones and flavonoid derivatives. In our continuous search on Centaurea genus, a phytochemical study was performed on Centaurea polyclada DC., an endemic of West Anatolia. Previously undescribed two sesquiterpene-amino acid conjugates, an elemane and an eudesmane derivative were isolated from the aerial parts of Centaurea polyclada, together with eight known compounds; two elemane derivatives, three flavonoids, a lignan, a phenolic glucoside and a phenylpropanoid glucoside. Structural elucidation of the compounds was based on spectroscopic evidence, including 1D and 2D NMR and high-resolution mass spectrometry, chemical degradation results and reference data comparison. Sesquiterpene-amino acid conjugates are representatives of an unusual group of sesquiterpenes, and elemane-amino acid conjugates are herein reported for the first time in nature.
- Demir, Serdar,Karaalp, Canan,Bedir, Erdal
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- Asymmetric Transformations of Proline and 2-Piperidinecarboxylic Acid via Formation of Salts with Optically Active Tartaric Acid
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The rates of racemization of optically active proline and 2-piperidinecarboxylic acid by using aldehydes as a catalyst tended to increase with a decrease in the acidity of the carboxylic acid used as solvent.Based on these results, the asymmetric transformations of DL-Pro and (RS)-Pia were carried out via formation of salts with (2R,3R)-tartaric acid to give optically pure L-Pro in over 80percent yield and (R)-Pia in 70percent yield.The asymmetric transformation of L-Pro was more successfully achieved by using (2S,3S)-tartaric acid to give optically pure D-Pro in 85percent yield based on the starting L-Pro.
- Shiraiwa, Tadashi,Shinjo, Kazuyuki,Kurokawa, Hidemoto
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- Jahanyne, an apoptosis-inducing lipopeptide from the marine cyanobacterium lyngbya sp.
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An acetylene-containing lipopeptide, jahanyne, was isolated from the marine cyanobacterium Lyngbya sp. Its gross structure was established by spectroscopic analyses, and the absolute configuration was clarified based on a combination of chiral HPLC analyses, spectroscopic analyses, and derivatization reactions. Jahanyne significantly inhibited the growth of human cancer cells and induced apoptosis in HeLa cells.
- Iwasaki, Arihiro,Ohno, Osamu,Sumimoto, Shinpei,Ogawa, Hidetoshi,Nguyen, Kim Anh,Suenaga, Kiyotake
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- Apratoxin E, a cytotoxic peptolide from a guamanian collection of the marine cyanobacterium Lyngbya bouillonii
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A collection of the marine cyanobacterium Lyngbya bouillonii from Guam afforded apratoxin E (1), a new peptide-polyketide hybrid of the apratoxin class of cytotoxins. The planar structure of 1 was elucidated by NMR spectroscopic analysis and mass spectrometry. Configurational assignments of stereocenters in the peptide portion were made by chiral HPLC analysis of the acid hydrolysate. The relative configuration in the polyketide moiety was assigned by comparison of NMR data including proton-proton coupling constants with those of the known analogues. Apratoxin E (1) displayed strong cytotoxicity against several cancer cell lines derived from colon, cervix, and bone, ranging from 21 to 72 nM, suggesting that the α,β-unsaturation of the modified cysteine residue is not essential for apratoxin activity. The 5- to 15-fold reduced activity compared with apratoxin A (2) is attributed to the dehydration in the long-chain polyketide unit, which could affect the conformation of the molecule.
- Matthew, Susan,Schupp, Peter J.,Luesch, Hendrik
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- STRUCTURE OF CYCLOTHIAZOMYCIN, A UNIQUE POLYTHIAZOLE-CONTAINING PEPTIDE WITH RENIN INHIBITORY ACTIVITY. PART 1. CHEMISTRY AND PARTIAL STRUCTURES OF CYCLOTHIAZOMYCIN
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Cyclothiazomycin is a novel renin inhibitor produced by Streptomyces sp.NR 0516 (IC50 1.66μM).Its molecular formular was determined to be C59H64N18O14S7 (MW. 1472) based on high-resolution FAB mass and NMR spectroscopy.Five fragments of cyclothiazomycin containing thiazole, thiazoline, heterocyclic chromophore were clarified by extensive 2D-NMR experiments.
- Aoki, Masahiro,Ohtsuka, Tatsuo,Itezono, Yoshiko,Yokose, Kazuteru,Furihata, Kazuo,Seto, Haruo
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- Discovery of Amantamide, a Selective CXCR7 Agonist from Marine Cyanobacteria
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CXCR7 plays an emerging role in several physiological processes. A linear peptide, amantamide (1), was isolated from marine cyanobacteria, and the structure was determined by NMR and mass spectrometry. The total synthesis was achieved by solid-phase method. After screening two biological target libraries, 1 was identified as a selective CXCR7 agonist. The selective activation of CXCR7 by 1 could provide the basis for developing CXCR7-targeted therapeutics and deciphering the role of CXCR7 in different diseases.
- Liang, Xiao,Luo, Danmeng,Yan, Jia-Lei,Rezaei, Mohammad A.,Salvador-Reyes, Lilibeth A.,Gunasekera, Sarath P.,Li, Chenglong,Ye, Tao,Paul, Valerie J.,Luesch, Hendrik
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- Stylissamides e and F, cyclic heptapeptides from the caribbean sponge stylissa caribica
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In addition to the four known stylissamides, A (1), B (2), C, and D, two new cyclic heptapeptides, stylissamides E (3) and F (4), were isolated from the Caribbean sponge Stylissa caribica. The structures of 3 and 4 were elucidated from a combination of mass spectrometric and NMR spectroscopic data as cyclo-(cis-Pro1-Tyr2-trans-Pro3-Ala 4-Ile5-Gln6-Ile7) for stylissamide E (3) and cyclo-(trans-Pro1-cis-Pro2-Phe 3-Asp4-trans-Pro5-Arg6-Phe 7) for stylissamide F (4).
- Cychon, Christine,Koeck, Matthias
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- Ionic Liquids Derived from Proline: Application as Surfactants
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Ionic liquids derived from prolinium esters, previously described as fully green and stable, were found to decompose in the presence of water by ester hydrolysis. To avoid this problem, a new family of these biodegradable salts incorporating an alcohol instead of the ester group is proposed. From this family, two novel ionic liquids that incorporate the prolinolium cation [HOPro] and the [DS] or [DBS] anion were selected (DS=dodecylsulfate; DBS=dodecylbenzenesulfonate). Both salts are liquid at room temperature, a property not usually found in ionic surfactants, and are also chemically and thermally stable. Moreover, they are more effective in reducing the surface tension of water than the corresponding traditional surfactants in the form of sodium salts, being useful for applications related to their aggregation capacity. They were tested for surfactant enhanced oil recovery and an optimal formulation for reservoirs at high salinity and temperature, able to produce ultra-low interfacial tension, was found with [HOPro][DBS].
- Fernández-Stefanuto, Verónica,Corchero, Raquel,Rodríguez-Escontrela, Iria,Soto, Ana,Tojo, Emilia
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- Solid-phase syntheses of olefin-containing inhibitors for HTLV-1 protease using the Horner-Emmons reaction
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The solid-phase Horner-Emmons reaction was successfully applied for the convenient syntheses of olefin-containing protease inhibitors. The isomerization during the solid-phase Horner-Emmons reaction can be minimized simply by the use of an appropriate amount of the base. The synthesized olefin peptides, which have an olefin γ-amino acid at the scissile site, were found to act as effective inhibitors for the HTLV-1 protease for the first time.
- Bang, Jeong Kyu,Naka, Hiromi,Teruya, Kenta,Aimoto, Saburo,Konno, Hiroyuki,Nosaka, Kazuto,Tatsumi, Tadashi,Akaji, Kenichi
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- (-)/(+)-Sparteine induced chirally-active carbon nanoparticles for enantioselective separation of racemic mixtures
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Chiral carbon nanoparticles (CCNPs) were developed by surface passivation using the chiral ligand (-)-sparteine or (+)-sparteine (denoted (-)-SP/CNP and (+)-SP/CNP, respectively). The chirality of the prepared CCNPs was demonstrated by circular dichroism
- Vulugundam, Gururaja,Misra, Santosh K.,Ostadhossein, Fatemeh,Schwartz-Duval, Aaron S.,Daza, Enrique A.,Pan, Dipanjan
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- An angiogenesis inhibitor isolated from a marine-derived actinomycete, Nocardiopsis sp. 03N67
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Cyclo-(l-Pro-l-Met) was isolated from the fermentation broth of a marine-derived actinomycete Nocardiopsis sp. 03N67 by chromatographic analysis and showed anti-angiogenesis activity against human umbilical vein endothelial cells (HUVECs). The structure and absolute stereochemistry of this compound were determined based on extensive spectroscopic data analysis, and Marfey's method, respectively.
- Shin, Hee Jae,Mondol, M.A. Mojid,Yu, Tae Kyung,Lee, Hyi-Seung,Lee, Yeon-Ju,Jung, Hye Jin,Kim, Jong Hyeon,Kwon, Ho Jeong
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- Amino acid-sesquiterpene lactone conjugates from the aerial parts of Centaurea pungens and evaluation of their antimicrobial activity
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Two new amino acid-sesquiterpene lactone conjugates, named centaureolide A (1) and centaureolide B (2) along with a germacrane derivative (3), five flavonoids (4–8) and one quinic acid derivative (9) have been isolated from the aerial parts of Centaurea pungens (Asteraceae). Their structures were established by a combination of one- and two-dimensional NMR techniques, and mass spectrometry. The never reported sesquiterpene lactones have been determined as germacrane derivatives (1 and 2) characterized by the unusual occurrence of a proline moiety. In order to validate the use of the extract of C. pungens in folk medicine, the antimicrobial activity of the isolated compounds against the Gram-positive strains Bacillus cereus, Staphylococcus aureus and Listeria innocua and the Gram-negative strains Pseudomonas aeruginosa and Pseudomonas fragi was evaluated.
- Labed, Fatiha,Masullo, Milena,Mirra, Virginia,Nazzaro, Filomena,Benayache, Fadila,Benayache, Samir,Piacente, Sonia
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- Planktocyclin, a cyclooctapeptide protease inhibitor produced by the freshwater cyanobacterium Planktothrix rubescens
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The freshwater cyanobacterium Planktothrix rubescens produces the cyclooctapeptide cyclo(Pro-Gly-Leu-Val-Met-Phe-Gly-Val). The chemical structure is new. This homodetic cyclic octapeptide was named planktocyclin (1). It consists solely of proteinogenic L-amino acids and is a strong inhibitor of mammalian trypsin and α-chymotrypsin and a moderately active inhibitor of human recombinant caspase-8. Mass spectrometric and 2D-NMR spectroscopic data allowed the determination of its structure. Synthetic planktocyclin was identical to the natural product.
- Baumann, Heike I.,Keller, Simone,Wolter, Falko E.,Nicholson, Graeme J.,Jung, Guenther,Suessmuth, Roderich D.,Juettner, Friedrich
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- Malyngamide 3 and cocosamides A and B from the marine cyanobacterium lyngbya majuscula from cocos lagoon, guam
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Malyngamide 3 (1) and cocosamides A (2) and B (3) were isolated from the lipophilic extract of a collection of Lyngbya majuscula from Cocos Lagoon, Guam. The planar structures of compounds 1-3 were determined by spectroscopic methods. The absolute configuration of 1 was determined by modified Mosher's method, NOESY data, and comparison with lyngbic acid (4). The absolute configurations of 2 and 3 were assigned by enantioselective HPLC analysis and comparison with the closely related compound pitipeptolide A (5). Compounds 1-3 showed weak cytotoxicity against MCF7 breast cancer and HT-29 colon cancer cells.
- Gunasekera, Sarath P.,Owle, Chivas S.,Montaser, Rana,Luesch, Hendrik,Paul, Valerie J.
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- Aestuaramides, a natural library of cyanobactin cyclic peptides resulting from isoprene-derived Claisen rearrangements
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We report 12 cyanobactin cyclic peptides, the aestuaramides, from the cultivated cyanobacterium Lyngbya aestuarii. We show that aestuaramides are synthesized enzymatically as reverse O-prenylated tyrosine ethers that subsequently undergo a Claisen rearrangement to produce forward C-prenylated tyrosine. These results reveal that a nonenzymatic Claisen rearrangement dictates isoprene regiochemistry in a natural system. They also reveal one of the mechanisms that organisms use to generate structurally diverse compound libraries starting from simple ribosomal peptide pathways (RiPPs).
- McIntosh, John A.,Lin, Zhenjian,Tianero, Ma. Diarey B.,Schmidt, Eric W.
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- Chromatographic method for the determination of conditional equilibrium constants for the carbamate formation reaction from amino acids and peptides in aqueous solution
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A novel and sensitive method has been developed and evaluated for the study of carbamate formation equilibria of amino acids and peptides in aqueous solution. The method is based on reversed-phase liquid chromatography with cetyltrimethylammonium bromide. The reliability of the method was established by comparing the results determined from the present study with the few data in the literature. The relaxation rate of the carbamate reaction was shown to be faster than the chromatographic distribution relaxation rate (seconds). As a result, the retention time of amine solutes is increased in the presence of CO2. Carbamate formation constants and mole fractions of carbamates at physiological pH of eleven L-α-amino acids and peptides were determined. No correlation between the formation constant and the ammonium pKa was found. There is significant dependence of the amount of a particular amino acid or peptide that exists as carbamate at pH 7.4 on the pKa of the ammonium group, however. This is due to mass action rather than reflecting the influence of pKa on the propensity of the amine to react with CO2. It is suggested that amino acids and peptides with ammonium pKa greater than 9.5 do not form significant amounts of carbamates in aqueous solution near neutral pH.
- Chen, Jian-Ge,Sandberg, Mats,Weber, Stephen G.
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- Biseokeaniamides A, B, and C, Sterol O-Acyltransferase Inhibitors from an Okeania sp. Marine Cyanobacterium
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Biseokeaniamides A, B, and C (1-3), structurally novel sterol O-acyltransferase (SOAT) inhibitors, were isolated from an Okeania sp. marine cyanobacterium. Their structures were elucidated by spectroscopic analyses and degradation reactions. Biseokeaniamide B (2) exhibited moderate cytotoxicity against human HeLa cancer cells, and compounds 1-3 inhibited both SOAT1 and SOAT2, not only at an enzyme level but also at a cellular level. Biseokeaniamides (1-3) are the first linear lipopeptides that have been shown to exhibit SOAT-inhibitory activity.
- Iwasaki, Arihiro,Tadenuma, Takato,Sumimoto, Shimpei,Ohshiro, Taichi,Ozaki, Kaori,Kobayashi, Keisuke,Teruya, Toshiaki,Tomoda, Hiroshi,Suenaga, Kiyotake
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- Urumamide, a novel chymotrypsin inhibitor with a β-amino acid from a marine cyanobacterium Okeania sp.
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Urumamide, a novel cyclic depsipeptide that contains a β-amino acid, was isolated from a marine cyanobacterium Okeania sp. Its gross structure was determined by spectroscopic analyses, and the absolute configuration was established based on Marfey's analyses and chiral HPLC analyses of hydrolysis products. Biologically, urumamide inhibited the growth of human cancer cells. In addition, urumamide inhibited chymotrypsin.
- Kanamori, Yuki,Iwasaki, Arihiro,Sumimoto, Shinpei,Suenaga, Kiyotake
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- Odobromoamide, a terminal alkynyl bromide-containing cyclodepsipeptide from the marine cyanobacterium okeania sp.
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The bioassay-guided fractionation of the Okinawan marine cyanobacterium Okeania sp. led to the isolation of the novel cyclodepsipeptide odobromoamide (1). The gross structure of 1 was determined by spectroscopic analyses, and its absolute stereochemistry was determined using a variety of different methods, including chemical derivatization and degradation followed by HPLC analysis. In addition, odobromoamide (1) exhibited broad-spectrum cytotoxicity against a human cancer cell line panel.
- Sueyoshi, Kosuke,Kudo, Takafumi,Yamano, Aki,Sumimoto, Shimpei,Iwasaki, Arihiro,Suenaga, Kiyotake,Teruya, Toshiaki
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- Pitipeptolides C-F, antimycobacterial cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula from Guam
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Pitipeptolides A (1) and B (2) are cyclic depsipeptides isolated from the marine cyanobacterium Lyngbya majuscula from Piti Bomb Holes, Guam. Additional analogues have now been isolated by revisiting larger collections of the same cyanobacterium. The four identified analogues, pitipeptolides C-F (3-6), are the tetrahydro analogue (3), an analogue with a lower degree of methylation (4) as well as two homologues (5 and 6) of pitipeptolide A. Their structures were elucidated using 2D NMR experiments, chiral HPLC analysis and comparison with pitipeptolide A. The identified analogues showed weaker cytotoxic activities compared to the two major parent compounds, pitipeptolides A (1) and B (2), against HT-29 colon adenocarcinoma and MCF7 breast cancer cells. On the other hand, pitipeptolide F (6) was the most potent pitipeptolide in a disc diffusion assay against Mycobacterium tuberculosis. The latter finding suggests that the structure of pitipeptolides could be optimized for selective antibacterial activity.
- Montaser, Rana,Paul, Valerie J.,Luesch, Hendrik
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- Porpoisamides A and B, two novel epimeric cyclic depsipeptides from a Florida Keys collection of Lyngbya sp.
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NMR-guided fractionation of a non-polar extract of a Florida Keys collection of Lyngbya sp. resulted in the isolation of two novel epimeric cyclic depsipeptides, porpoisamides A (1) and B (2). The planar structures of these compounds were determined using NMR spectroscopic techniques. The absolute configurations of amino and hydroxy acid subunits were assigned by enantioselective HPLC analysis. These compounds showed weak cytotoxicity towards HCT-116 colorectal carcinoma and U2OS osteosarcoma cells. The porpoisamides are a unique pair of cyclic depsipeptides that are epimeric at C-2 of the β-amino acid, 3-amino-2-methyloctanoic acid.
- Meickle, Theresa,Gunasekera, Sarath P.,Liu, Yanxia,Luesch, Hendrik,Paul, Valerie J.
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- Segetalins B, C and D, Three New Cyclic Peptides from Vaccaria segetalis
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Three new cyclic peptides, segetalins B, C and D, were isolated from Vaccaria segetalis (seeds) and their structures were elucidated by 2D NMR and chemical degradations.Conformational analysis of segetalin B, having an estrogen-like effect, was made by using high field NMR and computational methods.Segetalin B was suggested to possess a solution conformation similar to that of segetalin A in the region of Trp-Ala-Gly-Val.The sequence and conformation of Trp-Ala-Gly-Val may play an important role to show the activity.
- Morita, Hiroshi,Yun, Young Sook,Takeya, Koichi,Itokawa, Hideji,Yamada, Kenji
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- Selective activation of organocatalysts by specific signals
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Reminiscent of signal transduction in biological systems, artificial catalysts whose activity can be controlled by physical or chemical signals would be of high interest in the design of chemical systems that can respond to their environment. Self-immolative chemistry offers a generic method for the development of catalysts that can be activated by different signals. To demonstrate the versatility of that concept, we synthesized organocatalysts that can be activated by three different signals and that can be used to control two different reactions. In this way the organocatalyst proline is designed as a pro-catalyst that is activated either by the chemical signal H2O2, by light or by the enzyme penicillin acylase. The pro-catalysts were used to exert temporal control over the rate of an aldol reaction and a Michael reaction.
- Maity, Chandan,Trausel, Fanny,Eelkema, Rienk
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- Cell-free biocatalytic syntheses of l-pipecolic acid: A dual strategy approach and process intensification in flow
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As an alternative to the traditional chemical synthesis or in vivo production of l-pipecolic acid, we have developed two ex vivo strategies using purified and immobilised enzymes for the production of this key building block. Firstly, a transaminase capable of lysine ?-deamination was coupled with a novel pyrroline-5-carboxylate reductase, yielding 60% conversion at the 50 mM scale with free enzymes and in situ recycling of the cofactor. A second, simpler, redox neutral system was then constructed by combining the pyrroline-5-carboxylate reductase with a lysine-6-dehydrogenase. This bienzymatic system, with catalytic amount of free cofactor yielded >99% of pipecolic acid in batch and, following co-immobilisation of both enzymes, it was applied as a packed-bed reactor in continuous flow achieving again a molar conversion of >99% with 30 min residence time, and a space-time yield up to 2.5 g L-1 h-1. The sustainability of the system was further improved by a catch-and-release strategy to purify the product, and recovery and recycling of the cofactor.
- Benítez-Mateos, Ana I.,Calvey, Liam,Paradisi, Francesca,Roura Padrosa, David
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- Squamins C–F, four cyclopeptides from the seeds of Annona globiflora
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Four cyclic octapeptides, squamins C–F, were isolated from the seeds of Annona globiflora Schltdl. These compounds share part of their amino acid sequence, -Pro-Met(O)-Tyr-Gly-Thr-, with previously reported squamins A and B. Their structures were determined using NMR spectroscopic techniques together with quantum mechanical calculations (QM-NMR), ESI-HRMS data and a modified version of Marfey's chromatographic method. All compounds showed cytotoxic activity against DU-145 (human prostate cancer) and HeLa (human cervical carcinoma) cell lines. Clearly, A. globiflora is an important source of bioactive molecules, which could promote the sustainable exploitation of this undervalued specie.
- Sosa-Rueda, Javier,Domínguez-Meléndez, Vanihamin,Ortiz-Celiseo, Araceli,López-Fentanes, Fernando C.,Cuadrado, Cristina,Fernández, José J.,Daranas, Antonio Hernández,Cen-Pacheco, Francisco
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- Direct monitoring of biocatalytic deacetylation of amino acid substrates by1H NMR reveals fine details of substrate specificity
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Amino acids are key synthetic building blocks that can be prepared in an enantiopure form by biocatalytic methods. We show that thel-selective ornithine deacetylase ArgE catalyses hydrolysis of a wide-range ofN-acyl-amino acid substrates. This activity was revealed by1H NMR spectroscopy that monitored the appearance of the well resolved signal of the acetate product. Furthermore, the assay was used to probe the subtle structural selectivity of the biocatalyst using a substrate that could adopt different rotameric conformations.
- De Cesare, Silvia,McKenna, Catherine A.,Mulholland, Nicholas,Murray, Lorna,Bella, Juraj,Campopiano, Dominic J.
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supporting information
p. 4904 - 4909
(2021/06/16)
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- Leveraging Peptaibol Biosynthetic Promiscuity for Next-Generation Antiplasmodial Therapeutics
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Malaria remains a worldwide threat, afflicting over 200 million people each year. The emergence of drug resistance against existing therapeutics threatens to destabilize global efforts aimed at controlling Plasmodium spp. parasites, which is expected to leave vast portions of humanity unprotected against the disease. To address this need, systematic testing of a fungal natural product extract library assembled through the University of Oklahoma Citizen Science Soil Collection Program has generated an initial set of bioactive extracts that exhibit potent antiplasmodial activity (EC50 25 μM, selectivity index > 250). The unique chemodiversity afforded by these fungal isolates serves to unlock new opportunities for translating peptaibols into a bioactive scaffold worthy of further development.
- Lee, Jin Woo,Collins, Jennifer E.,Wendt, Karen L.,Chakrabarti, Debopam,Cichewicz, Robert H.
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supporting information
p. 503 - 517
(2021/03/01)
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- Isolation, Structure Determination, and Total Synthesis of Hoshinoamide C, an Antiparasitic Lipopeptide from the Marine Cyanobacterium Caldora penicillata
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Hoshinoamide C (1), an antiparasitic lipopeptide, was isolated from the marine cyanobacterium Caldora penicillata. Its planar structure was elucidated by spectral analyses, mainly 2D NMR, and the absolute configurations of the α-amino acid moieties were determined by degradation reactions followed by chiral-phase HPLC analyses. To clarify the absolute configuration of an unusual amino acid moiety, we synthesized two possible diastereomers of hoshinoamide C and determined its absolute configuration based on a comparison of their spectroscopic data with those of the natural compound. Hoshinoamide C (1) did not exhibit any cytotoxicity against HeLa or HL60 cells at 10 μM, but inhibited the growth of the parasites responsible for malaria (IC50 0.96 μM) and African sleeping sickness (IC50 2.9 μM).
- Iwasaki, Arihiro,Ohtomo, Keisuke,Kurisawa, Naoaki,Shiota, Ikuma,Rahmawati, Yulia,Jeelani, Ghulam,Nozaki, Tomoyoshi,Suenaga, Kiyotake
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p. 126 - 135
(2021/01/13)
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- Genomics-driven discovery of a new cyclodepsipeptide from the guanophilic fungusAmphichorda guana
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Two potential non-ribosomal peptide synthetases (NRPSs) were identified in the genome of a guanophilic fungusAmphichorda guanaby bioinformatics analysis and gene knockout experiments. Liquid chromatography coupled with mass spectrometry (LC-MS) guided isolation led to the discovery of a new cyclodepsipeptide isaridin H (1) and seven known analogs, desmethylisaridin E (2), isaridin E (3), isariin A (4), iso-isariin B (5), iso-isariin D (6), isariin E (7), and nodupetide (8). The absolute configuration of isaridin H (1) was achieved by Marfey's method. Isaridin H (1) showed significant antifungal activity againstBotrytis cinereaandAlternaria solani.
- Liang, Min,Lyu, Hai-Ning,Ma, Zi-Ying,Li, Er-Wei,Cai, Lei,Yin, Wen-Bing
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p. 1960 - 1964
(2021/03/16)
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- Motobamide, an Antitrypanosomal Cyclic Peptide from a Leptolyngbya sp. Marine Cyanobacterium
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Motobamide (1), a new cyclic peptide containing a C-prenylated cyclotryptophan residue, was isolated from a marine Leptolyngbya sp. cyanobacterium. Its planar structure was established by spectroscopic and MS/MS analyses. The absolute configuration was elucidated based on a combination of chemical degradations, chiral-phase HPLC analyses, spectroscopic analyses, and computational chemistry. Motobamide (1) moderately inhibited the growth of bloodstream forms of Trypanosoma brucei rhodesiense (IC50 2.3 μM). However, it exhibited a weaker cytotoxicity against normal human cells (IC50 55 μM).
- Iwasaki, Arihiro,Jeelani, Ghulam,Kurisawa, Naoaki,Matsubara, Teruhiko,Nozaki, Tomoyoshi,Sato, Toshinori,Suenaga, Kiyotake,Suzuki, Ryota,Takahashi, Hiroki
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p. 1649 - 1655
(2021/05/29)
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- Argicyclamides A-C Unveil Enzymatic Basis for Guanidine Bis-prenylation
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Guanidine prenylation is an outstanding modification in alkaloid and peptide biosynthesis, but its enzymatic basis has remained elusive. We report the isolation of argicyclamides, a new class of cyanobactins with unique mono- and bis-prenylations on guanidine moieties, from Microcystis aeruginosa NIES-88. The genetic basis of argicyclamide biosynthesis was established by the heterologous expression and in vitro characterization of biosynthetic enzymes including AgcF, a new guanidine prenyltransferase. This study provides important insight into the biosynthesis of prenylated guanidines and offers a new toolkit for peptide modification.
- Balloo, Nandani,Fujita, Kei,Matsuda, Kenichi,Okino, Tatsufumi,Phan, Chin-Soon,Wakimoto, Toshiyuki
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supporting information
p. 10083 - 10087
(2021/07/26)
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- Synthesis method of vildagliptin
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The invention discloses a synthesis method of vildagliptin. The method comprises the following steps: performing esterification reaction on L-glutamic acid and ethanol to obtain L-glutamic acid-gamma-ethyl ester; reducing the L-glutamic acid-gamma-ethyl ester under the action of potassium borohydride to obtain L-proline; mixing L-proline with ethyl chloroformate for reaction to obtain acid anhydride; further reacting the acid anhydride with amine to obtain amide; dehydrating the amide under the action of phosphorus pentoxide to obtain an intermediate 1; performing substitution reaction on theintermediate 1 and chloroacetyl chloride to obtain an intermediate 2; and further reacting the intermediate 2 with 3-amino-1-adamantanol to obtain vildagliptin. The method has the advantages that fewimpurities are generated in the vildagliptin preparation process, the yield of the prepared vildagliptin is high, and compared with the prior art, the process is simpler, and the vildagliptin preparation cost is greatly reduced.
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- Iheyamides A-C, Antitrypanosomal Linear Peptides Isolated from a Marine Dapis sp. Cyanobacterium
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Iheyamides A (1), B (2), and C (3), new linear peptides, were isolated from a marine Dapis sp. cyanobacterium. Their structures were elucidated by spectroscopic analyses and degradation reactions. Iheyamide A (1) showed moderate antitrypanosomal activities against Trypanosoma brucei rhodesiense and Trypanosoma brucei brucei (IC50 = 1.5 μM), but the other two analogues, iheyamides B (2) and C (3), did not (IC50 > 20 μM, respectively). The structure-activity relationship clarified that an isopropyl-O-Me-pyrrolinone moiety was necessary for the antitrypanosomal activity. Furthermore, the cytotoxicity of 1 against normal human cells, WI-38, was 10 times weaker than its antitrypanosomal activity (IC50 = 18 μM).
- Kurisawa, Naoaki,Iwasaki, Arihiro,Jeelani, Ghulam,Nozaki, Tomoyoshi,Suenaga, Kiyotake
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p. 1684 - 1690
(2020/06/08)
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- Krisynomycins, Imipenem Potentiators against Methicillin-Resistant Staphylococcus aureus, Produced by Streptomyces canus
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A reinvestigation of the acetone extract of the strain CA-091830 of Streptomyces canus, producer of the imipenem potentiator krisynomycin, resulted in the isolation of two additional analogues, krisynomycins B (1) and C (2), with different chlorination patterns. Genome sequencing of the strain followed by detailed bioinformatics analysis led to the identification of the corresponding biosynthetic gene cluster (BGC) of this cyclic nonribosomal peptide family. The planar structure of the new molecules was determined using HRMS, ESI-qTOF-MS/MS, and 1D and 2D NMR data. Their absolute configuration was proposed using a combination of Marfey's and bioinformatic BGC analyses. The krisynomycins displayed weak to negligible antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA), which was significantly enhanced when tested in combination with sublethal concentrations of imipenem. The halogenation pattern plays a key role in the antimicrobial activity and imipenem-potentiating effects of the compounds, with molecules having a higher number of chlorine atoms potentiating the effect of imipenem at lower doses.
- De La Cruz, Mercedes,Genilloud, Olga,González, Ignacio,Martín, Jesús,Oves-Costales, Daniel,Pérez-Bonilla, Mercedes,Reyes, Fernando,Vicente, Francisca
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p. 2597 - 2606
(2020/10/12)
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- Integrating Biomass into the Organonitrogen Chemical Supply Chain: Production of Pyrrole and d-Proline from Furfural
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Production of renewable, high-value N-containing chemicals from lignocellulose will expand product diversity and increase the economic competitiveness of the biorefinery. Herein, we report a single-step conversion of furfural to pyrrole in 75 % yield as a key N-containing building block, achieved via tandem decarbonylation–amination reactions over tailor-designed Pd?S-1 and H-beta zeolite catalytic system. Pyrrole was further transformed into dl-proline in two steps following carboxylation with CO2 and hydrogenation over Rh/C catalyst. After treating with Escherichia coli, valuable d-proline was obtained in theoretically maximum yield (50 %) bearing 99 % ee. The report here establishes a route bridging commercial commodity feedstock from biomass with high-value organonitrogen chemicals through pyrrole as a hub molecule.
- Di, Lu,Fung Kin Yuen, Vincent,Song, Song,Sun, Qiming,Yan, Ning,Zhou, Kang
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supporting information
p. 19846 - 19850
(2020/09/02)
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- Basicities and Nucleophilicities of Pyrrolidines and Imidazolidinones Used as Organocatalysts
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The Br?nsted basicities pKaH (i.e., pKa of the conjugate acids) of 32 pyrrolidines and imidazolidinones, commonly used in organocatalytic reactions, have been determined photometrically in acetonitrile solution using CH acids as indicators. Most investigated pyrrolidines have basicities in the range 16 aH aH aH 12.6) and the 2-imidazoliummethyl-substituted pyrrolidine A21 (pKaH 11.1) are outside the typical range for pyrrolidines with basicities comparable to those of imidazolidinones. Kinetics of the reactions of these 32 organocatalysts with benzhydrylium ions (Ar2CH+) and structurally related quinone methides, common reference electrophiles for quantifying nucleophilic reactivities, have been measured photometrically. Most reactions followed second-order kinetics, first order in amine and first order in electrophile. More complex kinetics were observed for the reactions of imidazolidinones and several pyrrolidines carrying bulky 2-substituents, due to reversibility of the initial attack of the amines at the electrophiles followed by rate-determining deprotonation of the intermediate ammonium ions. In the presence of 2,4,6-collidine or 2,6-di-tert-butyl-4-methyl-pyridine, the deprotonation of the initial adducts became faster, which allowed the rate of the attack of the amines at the electrophiles to be determined. The resulting second-order rate constants k2 followed the correlation log?k2(20 °C) = sN(N + E), where electrophiles are characterized by one parameter (E) and nucleophiles are characterized by the two solvent-dependent parameters N and sN. In this way, the organocatalysts A1-A32 were integrated in our comprehensive nucleophilicity scale, which compares n-, -, and σ-nucleophiles. The nucleophilic reactivities of the title compounds correlate only poorly with their Br?nsted basicities.
- An, Feng,Maji, Biplab,Min, Elizabeth,Ofial, Armin R.,Mayr, Herbert
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supporting information
p. 1526 - 1547
(2020/02/04)
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- Caged Proline in Photoinitiated Organocatalysis
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Organocatalysis is an emerging field, in which small metal-free organic structures catalyze a diversity of reactions with a remarkable stereoselectivity. The ability to selectively switch on such pathways upon demand has proven to be a valuable tool in biological systems. Light as a trigger provides the ultimate spatial and temporal control of activation. However, there have been limited examples of phototriggered catalytic systems. Herein, we describe the synthesis and application of a caged proline system that can initiate organocatalysis upon irradiation. The caged proline was generated using the highly efficient 4-carboxy-5,7-dinitroindolinyl (CDNI) photocleavable protecting group in a four-step synthesis. Advantages of this system include water solubility, biocompatibility, high quantum yield for catalyst release, and responsiveness to two-photon excitation. We showed the light-triggered catalysis of a crossed aldol reaction, a Mannich reaction, and a self-aldol condensation reaction. We also demonstrated light-initiated catalysis, leading to the formation of a biocide in situ, which resulted in the growth inhibition of E. coli, with as little as 3 min of irradiation. This technique can be broadly applied to other systems, by which the formation of active forms of drugs can be catalytically assembled remotely via two-photon irradiation.
- Guruge, Charitha,Rfaish, Saad Y.,Byrd, Chanel,Yang, Shukun,Starrett, Anthony K.,Guisbert, Eric,Nesnas, Nasri
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p. 5236 - 5244
(2019/05/10)
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- Cyclic tetrapeptides from the marine strain Streptomyces sp. PNM-161a with activity against rice and yam phytopathogens
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Two cyclotetrapeptides, henceforth named Provipeptides A (1) and B (2), along with five known diketopiperazines (3–7) were isolated from the liquid culture of marine Streptomyces sp. 161a recovered from a sample of sea grass Bryopsis sp. The structures of cyclotetrapeptides and diketopiperazines (DKPs) were established by 1D and 2D NMR data, MS, and by comparison with literature data. The absolute stereochemistry of compounds cyclo-(l-Pro-l-Leu-d-Pro-l-Phe) 1 and cyclo-(-Pro-Ile-Pro-Phe) 2 was established by the Marfey’s method. Compound 1 showed antibacterial activity against rice phytopathogenic strains Burkholderia glumae (MIC = 1.1 mM) and Burkholderia gladioli (MIC = 0.068 mM), compound 2 was active only against B. glumae (MIC = 1.1 mM), and DKP cyclo-[l-Pro-l-Leu] 5 showed to be active against B. gladioli (MIC = 0.3 mM) and B. glumae (MIC = 2.4 mM). Compounds 1 and 2 showed 65% and 50% inhibition of Colletotrichum gloeosporioides (yam pathogen) conidia germination, respectively at a concentration of 1.1 mM.
- Betancur, Luz A.,Forero, Abel M.,Romero-Otero, Adriana,Sepúlveda, Lady Yohanna,Moreno-Sarmiento, Nubia C.,Castellanos, Leonardo,Ramos, Freddy A.
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p. 744 - 751
(2019/07/05)
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- Isolation and structure elucidation of cyclopeptide alkaloids from the leaves of Heisteria parvifolia
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Heisteria parvifolia Sm. is prescribed in traditional medecine against numerous diseases in C?te d'Ivoire. Due to the shortcoming in scientifical knowledge of use of this species, our investigations revealed five undescribed cyclopeptide alkaloids added to one known derivative namely anorldianine. These compounds were elucidated by 1D and 2D-NMR experiments and comparison with literature data, and confirmed by HR-ESI-MS. Cytotoxic activity evaluation of these compounds against the chronic myeloid leukemia (K565) cell line exhibited an antiproliferative activity with cell growth inhibition from 13% to 46%.
- Bitchi, Michel Boni,Magid, Abdulmagid Alabdul,Kabran, Faustin Aka,Yao-Kouassi, Philomène Akoua,Harakat, Dominique,Morjani, Hamid,Tonzibo, Félix Zanahi,Voutquenne-Nazabadioko, Laurence
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- Isolation and Total Synthesis of Mabuniamide, a Lipopeptide from an Okeania sp. Marine Cyanobacterium
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The bioassay-guided fractionation of an Okeania sp. marine cyanobacterium collected in Okinawa led to the isolation of the lipopeptide mabuniamide (1). The gross structure of 1 was determined by spectroscopic analyses, and its absolute configuration was determined using Marfey's analysis of the acid hydrolysate of 1. The absolute configuration of 1 was confirmed by total synthesis. Mabuniamide (1) stimulated glucose uptake in cultured rat L6 myotubes. In addition, mabuniamide (1) and its stereoisomer (2) exhibited moderate antimalarial activity.
- Ozaki, Kaori,Iwasaki, Arihiro,Sezawa, Dai,Fujimura, Haruka,Nozaki, Tomoyoshi,Saito-Nakano, Yumiko,Suenaga, Kiyotake,Teruya, Toshiaki
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p. 2907 - 2915
(2019/10/16)
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- Viriditins from Byssochlamys spectabilis, their stereochemistry and biosynthesis
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Byssochlamys spectabilis (anamorph Paecilomyces variotii) strain 10536 was isolated as an endophyte from grapevine and investigated for its secondary metabolite production. Cultures of B. spectabilis yielded the known compound viriditin A (1) and its new derivative viriditin B (2), which showed pronounced cis–trans-amide isomerism. The previously unknown absolute configuration of C–2 and C–13 in 1 were assigned by Mosher's method. Marfey's method confirmed 2S stereochemistry after Jones oxidation and hydrolysis. A series of feeding experiments with [1-13C], [2-13C] and [1, 2-13C2]-acetate as well as [methyl-13C]-methionine indicated a polyketide biosynthetic pathway. Compound 1 showed weak cytotoxicity against the cell line KB3.1 with an IC50 = 30 μg/ml.
- Campisano, Andrea,López-Fernández, Sebastián,Schulz, Barbara J.,Stadler, Marc,Steinert, Michael,Surup, Frank
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supporting information
(2019/12/25)
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- Cytotoxic and antimicrobial compounds from the marine-derived fungus, penicillium species
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The organic extract of liquid cultures of the marine-derived Penicillium sp. was investigated. Fractionation of the extracts of the fungus led to the purification and identification of two new compounds, penicillatides A (1) and B (2), together with the previously reported cyclo(R-Pro–S-Phe) (3) and cyclo(R-Pro–R-Phe) (4). The structures of compounds 1–4 were assigned by extensive interpretation of their NMR and high-resolution mass spectrometry (HRMS). The antiproliferative and cytotoxic activities of the compounds against three human cancer cell lines as well as their antimicrobial activity against several pathogens were evaluated. Compounds 2–4 displayed variable cytotoxic and antimicrobial activities.
- Youssef, Diaa T. A.,Alahdal, Abdulrahman M.
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- Croissamide, a proline-rich cyclic peptide with an N-prenylated tryptophan from a marine cyanobacterium Symploca sp.
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Croissamide, a proline-rich cyclic peptide that contains an N-prenylated tryptophan, was isolated from a marine cyanobacterium Symploca sp. Its gross structure was determined by spectroscopic analyses, and the absolute configuration was established based on chiral HPLC analyses of acid hydrolysates.
- Iwasaki, Keitaro,Iwasaki, Arihiro,Sumimoto, Shimpei,Sano, Takuya,Hitomi, Yuki,Ohno, Osamu,Suenaga, Kiyotake
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supporting information
p. 3806 - 3809
(2018/09/17)
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- Chromatographic Resolution of α-Amino Acids by (R)-(3,3'-Halogen Substituted-1,1'-binaphthyl)-20-crown-6 Stationary Phase in HPLC
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Three new chiral stationary phases (CSPs) for high-performance liquid chromatography were prepared from R-(3,3'-halogen substituted-1,1'-binaphthyl)-20-crown-6 (halogen = Cl, Br and I). The experimental results showed that R-(3,3'-dibromo-1,1'-binaphthyl)-20-crown-6 (CSP-1) possesses more prominent enantioselectivity than the two other halogen-substituted crown ether derivatives. All twenty-one α-amino acids have different degrees of separation on R-(3,3'-dibromo-1,1'-binaphthyl)-20-crown-6-based CSP-1 at room temperature. The enantioselectivity of CSP-1 is also better than those of some commercial R-(1,1'-binaphthyl)-20-crown-6 derivatives. Both the separation factors (α) and the resolution (Rs) are better than those of commercial crown ether-based CSPs [CROWNPAK CR(+) from Daicel] under the same conditions for asparagine, threonine, proline, arginine, serine, histidine and valine, which cannot be separated by commercial CR(+). This study proves the commercial usefulness of the R-(3,3'-dibromo-1,1'-binaphthyl)-20-crown-6 chiral stationary phase.
- Wu, Peng,Wu, Yuping,Zhang, Junhui,Lu, Zhenyu,Zhang, Mei,Chen, Xuexian,Yuan, Liming
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supporting information
p. 1037 - 1042
(2017/07/25)
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- Tetrabutylammonium Fluoride as a Mild and Versatile Reagent for Cleaving Boroxazolidones to Their Corresponding Free α-Amino Acids
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Protection of α-amino acids with 9-borabicyclo[3.3.1]nonane (9-BBN) to give their corresponding boroxazolidones is highly attractive, as it concurrently masks both the amino and the carboxylic acid functionalities. However, the harsh methods required for deprotection of these boroxazolidones have limited their use. Herein, we report that tetrabutylammonium fluoride serves as a mild and versatile reagent that can be used to cleave boroxazolidones to their corresponding free α-amino acids. The reaction conditions were explored, including the use of various nucleophilic fluoride sources, solvents, and reaction temperatures. Nucleophilic fluoride sources comprising an ammonium cation proved superior to other countercations. The scope of the reaction was extended to the cleavage of B,B-diphenyl- and B,B-diethyl boroxazolidone complexes. Furthermore, a wide range of α-amino acid side-chain functionalities were shown to be compatible, including acids, esters, amides, thiols, thioethers, alkynes, phenols, basic heterocycles, and important biorelevant molecules such as glutathione, (S)-adenosyl-l-homocysteine, and l-biocytin.
- Poulie, Christian B. M.,Bunch, Lennart
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supporting information
p. 1475 - 1478
(2017/04/01)
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- Octaminomycins A and B, cyclic octadepsipeptides active against Plasmodium falciparum
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Two new cyclic octadepsipeptides, octaminomycins A (1) and B (2), were isolated from a microbial metabolite fraction library of Streptomyces sp. RK85-270 based on Natural Products Plot screening. Their structures were elucidated on the basis of HRESIMS, 1D and 2D NMR spectroscopic data, and MS/MS experiments for sequence analysis. The absolute configurations of the constituent amino acid residues were determined by a combination of single-crystal X-ray diffraction and Marfey's methodology. Notably, octaminomycins A (1) and B (2) showed good in vitro antiplasmodial activity against chloroquine-sensitive as well as chloroquine-resistant strains with no cytotoxicity up to 30 μM. (Chemical Equation Presented).
- Jang, Jun-Pil,Nogawa, Toshihiko,Futamura, Yushi,Shimizu, Takeshi,Hashizume, Daisuke,Takahashi, Shunji,Jang, Jae-Hyuk,Ahn, Jong Seog,Osada, Hiroyuki
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p. 134 - 140
(2017/02/05)
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- Stylissamide I, a new cyclic heptapeptide from an okinawan marine sponge Stylissa sp.
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A new cyclic heptapeptide, stylissamide I (1), was isolated from an Okinawan marine sponge Stylissa sp. The structure of stylissamide I (1) was elucidated to be cyclo-(L-Tyr1-L-Tyr2-L-Tyr3-L-Pro1-L-Pro2-L-Val-L-Pro3) by extensive spectral analyses and Marfey's method. Stylissamide I (1) showed antifungal activity against Aspergillus Niger.
- Kubota, Takaaki,Nakamura, Kenta,Kurimoto, Shin-Ichiro,Sakai, Kanae,Fromont, Jane,Gonoi, Tohru,Kobayashi, Jun'ichi
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p. 799 - 806
(2017/07/28)
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- Antibacterial low-molecular-weight compounds produced by the marine bacterium Rheinheimera japonica KMM 9513T
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Strain KMM 9513T was isolated from a sediment sample collected from the Sea of Japan seashore and selected due to its ability to inhibit indicator bacterial growth. The strain KMM 9513T has been recently described as a novel species Rheinheimera japonica. This study was undertaken to determine which substances produced by strain KMM 9513T could be responsible for its antimicrobial activity. Eight compounds were obtained from an ethyl acetate extract of R. japonica KMM 9513T. The structures of five diketopiperazines (4–8) and diisobutyl-, dibutyl- and bis(2-ethylhexyl) phthalates (1–3) were established on the basis of detailed interpretation of NMR data, by Marfey method and optical rotation data. The structures of diketopiperazines were determined as cyclo-(l-valyl-l-proline), cyclo-(l-valyl-d-proline), cyclo-(l-phenylalanyl-l-proline), cyclo-(l-leucyl-l-proline), and cyclo-(l-phenylalanyl-d-proline). Compounds 1–3, 5 and 8 revealed antimicrobial activities against Bacillus subtilis and/or Enterococcus faecium and Staphylococcus aureus. In this paper, we describe the isolation and structural elucidation of the isolated compounds 1–8. This is the first report of the characterisation of low molecular weight antibacterial metabolites produced by a member of the genus Rheinheimera.
- Kalinovskaya, Natalia I.,Romanenko, Lyudmila A.,Kalinovsky, Anatoly I.
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p. 719 - 726
(2017/04/14)
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- Purification, structural characterization and bioactivity evaluation of a novel proteoglycan produced by Corbicula fluminea
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A novel proteoglycan, named CFPS-11, was isolated from Corbicula fluminea, which is a food source of freshwater bivalve mollusk. CFPS-11 had an average molecular weight of 807.7 kDa and consisted of D-glucose and D-glucosamine in a molar ratio of 12.2:1.0. The protein moiety (～5%) of CFPS-11 was covalently bonded to the polysaccharide chain in O-linkage type through both serine and thereonine residues. The polysaccharide chain of CFPS-11 was composed of (1 → 4)-α-D-glucopyranosyl and (1 → 3,6)-α-D-glucopyranosyl residues, which branched at O-6. The branch chain consisted of (1 →)-α-D-glucopyranosyl and (1 →)-α-D-N-acetylglucosamine residues. CFPS-11 exhibited significant antioxidant activity in a dose-dependent manner and remarkable inhibition activities against α-amylase and α-glucosidase by in vitro assays. These findings indicated that the CFPS-11 from C. fluminea has the potential for development as a health food ingredient.
- Yan, Jing-Kun,Wang, Yao-Yao,Qiu, Wen-Yi,Wu, Li-Xia,Ding, Zhi-Chao,Cai, Wu-Dan
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- A novel thyroglobulin-binding lectin from the brown alga Hizikia fusiformis and its antioxidant activities
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A lectin (HFL) was isolated from the brown alga, Hizikia fusiformis, through ion exchange on cellulose DE52 and HPLC with a TSK-gel G4000PWXL column. SDS-PAGE showed that HFL had a molecular mass of 16.1 kDa. The HPLC (with a TSK-gel G4000PWXL column) indicated that HFL is a tetramer in its native state. The total carbohydrate content was 41%. Glucose, galactose and fucose were the monosaccharide units of HFL, and the normalized mol% values were 6, 14 and 80, respectively. HFL contains a large amount of the acidic amino acid, Asx. The β-elimination reaction suggested that the oligosaccharide and peptide moieties of HFL may belong to the N-glucosidic linkage. The amino acid sequences, of about five segments of HFL, were acquired by MALDI-TOF/TOF, and the sequences have no homology with other lectins. HFL was found to agglutinate sheep erythrocytes. The hemagglutination activity was inhibited by thyroglobulin, from bovine thyroid, but not by any of the monosaccharides tested. The lectin reaction was independent of the presence of the divalent cation Ca2+. HFL showed free radical scavenging activity against hydroxyl, DPPH and ABTS+ radicals.
- Wu, Mingjiang,Tong, Changqing,Wu, Yue,Liu, Shuai,Li, Wei
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- Variochelins, Lipopeptide Siderophores from Variovorax boronicumulans Discovered by Genome Mining
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Photoreactive siderophores have a major impact on the growth of planktonic organisms. To date, these molecules have mainly been reported from marine bacteria, although evidence is now accumulating that some terrestrial bacteria also harbor the biosynthetic potential for their production. In this paper, we describe the genomics-driven discovery and characterization of variochelins, lipopeptide siderophores from the bacterium Variovorax boronicumulans, which thrives in soil and freshwater habitats. Variochelins are different from most other lipopeptide siderophores in that their biosynthesis involves a polyketide synthase. We demonstrate that the ferric iron complex of variochelin A possesses photoreactive properties and present the MS-derived structures of two degradation products that emerge upon light exposure.
- Kurth, Colette,Schieferdecker, Sebastian,Athanasopoulou, Kalliopi,Seccareccia, Ivana,Nett, Markus
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p. 865 - 872
(2016/05/24)
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- New cyclotetrapeptides and a new diketopiperzine derivative from the marine sponge-associated fungus Neosartorya glabra KUFA 0702
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Two new cyclotetrapeptides, sartoryglabramides A (5) and B (6), and a new analog of fellutanine A (8) were isolated, together with six known compounds including ergosta-4, 6, 8 (14), 22-tetraen-3-one, ergosterol 5, 8-endoperoxide, helvolic acid, aszonalenin (1), (3R)-3-(1H-indol-3-ylmethyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione (2), takakiamide (3), (11aR)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione (4), and fellutanine A (7), from the ethyl acetate extract of the culture of the marine sponge-associated fungus Neosartorya glabra KUFA 0702. The structures of the new compounds were established based on extensive 1D and 2D spectral analysis. X-ray analysis was also used to confirm the relative configuration of the amino acid constituents of sartoryglabramide A (5), and the absolute stereochemistry of the amino acid constituents of sartoryglabramide A (5) and sartoryglabramides B (6) was determined by chiral HPLC analysis of their hydrolysates by co-injection with the D- and L- amino acids standards. Compounds 1-8 were tested for their antibacterial activity against Gram-positive (Escherichia coli ATCC 25922) and Gram-negative (Staphyllococus aureus ATCC 25923) bacteria, as well as for their antifungal activity against filamentous (Aspergillus fumigatus ATCC 46645), dermatophyte (Trichophyton rubrum ATCC FF5) and yeast (Candida albicans ATCC 10231). None of the tested compounds exhibited either antibacterial (MIC > 256 μg/mL) or antifungal activities (MIC > 512 μg/mL).
- Zin, War War May,Buttachon, Suradet,Dethoup, Tida,Fernandes, Carla,Cravo, Sara,Pinto, Madalena M. M.,Gales, Luís,Pereira, José A.,Silva, Artur M. S.,Sekeroglu, Nazim,Kijjoa, Anake
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- LITHIUM CO-CRYSTALS FOR TREATMENT OF NEUROPSYCHIATRIC DISORDERS
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The invention concerns methods and compositions for treating a neuropsychiatric disorder, wherein the method comprises administering an effective amount of a co-crystal of lithium to a subject in need thereof, wherein the co-crystal comprises lithium, or a pharmaceutically acceptable salt thereof, and an amino acid.
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- Janadolide, a Cyclic Polyketide-Peptide Hybrid Possessing a tert-Butyl Group from an Okeania sp. Marine Cyanobacterium
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Janadolide, a new cyclic polyketide-peptide hybrid possessing a tert-butyl group, was isolated from an Okeania sp. marine cyanobacterium. The gross structure was elucidated by spectroscopic analyses, and the absolute configurations of the amino acid moieties were determined by acid hydrolysis and chiral-phase HPLC analyses. The absolute configuration of the two stereogenic centers in the polyketide moiety was elucidated based on a combination of degradation reactions and spectroscopic analyses including the phenyl-glycine methyl ester method. Janadolide showed potent antitrypanosomal activity with an IC50 value of 47 nM without cytotoxicity against human cells at 10 μM.
- Ogawa, Hidetoshi,Iwasaki, Arihiro,Sumimoto, Shinpei,Kanamori, Yuki,Ohno, Osamu,Iwatsuki, Masato,Ishiyama, Aki,Hokari, Rei,Otoguro, Kazuhiko,Omura, Satoshi,Suenaga, Kiyotake
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p. 1862 - 1866
(2016/08/02)
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- Rapid, effective deprotection of tert-butoxycarbonyl (Boc) amino acids and peptides at high temperatures using a thermally stable ionic liquid
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A method for high temperature Boc deprotection of amino acids and peptides in a phosphonium ionic liquid is described. The ionic liquid had low viscosity, high thermal stability and demonstrated a beneficial effect. The study extended the possibility for extraction of water soluble polar organic molecules using ionic liquids. Trace water significantly improved product purity and yield, while only 2 equiv. TFA led to deprotection within 10 min. The trityl group was also deprotected.
- Bhawal, Sumit S.,Patil, Rahul A.,Armstrong, Daniel W.
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p. 95854 - 95856
(2015/11/24)
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- A protic ionic liquid catalyzed strategy for selective hydrolytic cleavage of tert-butyloxycarbonyl amine (N-Boc)
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A simple, mild and efficient strategy for selective hydrolytic cleavage of the N-tert-butyloxycarbonyl (Boc) group is devised using a protic ionic liquid as an efficient catalyst. The deprotection reaction proceeded well for N-Boc protected aromatic, heteroaromatic, aliphatic compounds, and chiral amino acid esters and peptides. A wide range of labile protecting groups such as tert-butyl ester, tert-butyl ether, benzyloxycarbonyl (Cbz), TBDMS, O-Boc and S-Boc remained unaffected under the reaction conditions. This journal is
- Majumdar, Swapan,De, Jhinuk,Chakraborty, Ankita,Roy, Dipanwita,Maiti, Dilip K.
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p. 3200 - 3205
(2015/02/03)
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- Characterization of two putative prolinases (PepR1 and PepR2) from Lactobacillus plantarum WCFS1: Occurrence of two isozymes with structural similarity and different catalytic properties
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Two putative prolinases (PepR1 and PepR2) of Lactobacillus plantarum WCSF1 share 48.5% amino acid sequence identity (55.5% at the DNA level); however, PepR1 exhibits over 80% identity at the protein level with other lactobacilli prolinases while PepR2 exhibits only 51% or less identity. In this study, the putative genes were overexpressed in Escherichia coli, purified to gel electrophoretic homogeneity, and then characterized. Purified PepR1 and PepR2 hydrolysed Pro-Xaa dipeptide substrates at similar rates, proving their nature as prolinases. Structural analyses using circular dichroism, dynamic light scattering, gel filtration, and molecular modelling revealed that the two prolinases have similar structural characteristics: high β-sheet content, homotetrameric structure, and similar folding to the PepI/PepL/PepR peptidase family. However, kinetic and thermodynamic analyses of PepR1 and PepR2 indicated differences in many aspects: optimum temperatures (25 and 30 °C, respectively), optimum pH (pH 7.5 and 8.0, respectively), substrate specificities (high stringency of PepR2), kinetic parameters, and thermal stability (29 and 48 °C, respectively). Also, these prolinases behaved differently towards inhibitor treatments, suggesting structural and/or functional differences in their active sites. Differences in the two prolinases would contribute to a diversity of catalytic activities, so that they work together cooperatively and complementarily to hydrolyse proline-containing peptides with broader specificity, working pH, working temperature, and higher efficiency, thus allowing adaptation to a wider range of environments.
- Huang, Yanyu,Tanaka, Takuji
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- An easy 'Filter-and-Separate' method for enantioselective separation and chiral sensing of substrates using a biomimetic homochiral polymer
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We present a polyfluorene appended with protected l-glutamic acid that exhibited a reversible α-helix/β-sheet-like conformation and helical porous fibrous morphology mimicking the super-structure of proteins. The new homochiral polymer probe enabled efficient heterogeneous enantioselective separation and chiral sensing of a wide variety of substrates from their aqueous racemic mixture using an easy 'Filter-and-Separate' method.
- Senthilkumar,Asha
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supporting information
p. 8931 - 8934
(2015/05/27)
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