- Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate-Directed Formation of Quinolones versus Quinazolinones
-
Previous studies showed that the FeII/α-ketoglutarate dependent dioxygenase AsqJ induces a skeletal rearrangement in viridicatin biosynthesis in Aspergillus nidulans, generating a quinolone scaffold from benzo[1,4]diazepine-2,5-dione substrates. We report that AsqJ catalyzes an additional, entirely different reaction, simply by a change in substituent in the benzodiazepinedione substrate. This new mechanism is established by substrate screening, application of functional probes, and computational analysis. AsqJ excises H2CO from the heterocyclic ring structure of suitable benzo[1,4]diazepine-2,5-dione substrates to generate quinazolinones. This novel AsqJ catalysis pathway is governed by a single substituent within the complex substrate. This unique substrate-directed reactivity of AsqJ enables the targeted biocatalytic generation of either quinolones or quinazolinones, two alkaloid frameworks of exceptional biomedical relevance.
- Einsiedler, Manuel,Jamieson, Cooper S.,Maskeri, Mark A.,Houk, Kendall N.,Gulder, Tobias A. M.
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supporting information
p. 8297 - 8302
(2021/03/01)
-
- Kras inhibitory cyclic peptide compound
-
The following were discovered: a cyclic peptide compound that interacts with Ras; and an unnatural amino acid that is useful in the production of said cyclic peptide compound. The cyclic peptide compound was also discovered to inhibit bonding between Ras and SOS. The following were additionally discovered: a specific unnatural amino acid included in said cyclic peptide compound; and a manufacturing method therefor.
- -
-
Paragraph 0682; 0821; 0824
(2021/06/03)
-
- Novel chiral stationary phases based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin combining cinchona alkaloid moiety
-
Novel chiral selectors based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin connecting quinine (QN) or quinidine (QD) moiety were synthesized and immobilized on silica gel. Their chromatographic performances were investigated by comparing to the 3,5-dimethyl phenylcarbamoylated β-cyclodextrin (β-CD) chiral stationary phase (CSP) and 9-O-(tert-butylcarbamoyl)-QN-based CSP (QN-AX). Fmoc-protected amino acids, chiral drug cloprostenol (which has been successfully employed in veterinary medicine), and neutral chiral analytes were evaluated on CSPs, and the results showed that the novel CSPs characterized as both enantioseparation capabilities of CD-based CSP and QN/QD-based CSPs have broader application range than β-CD-based CSP or QN/QD-based CSPs. It was found that QN/QD moieties play a dominant role in the overall enantioseparation process of Fmoc-amino acids accompanied by the synergistic effect of β-CD moiety, which lead to the different enantioseparation of β-CD-QN-based CSP and β-CD-QD-based CSP. Furthermore, new CSPs retain extraordinary enantioseparation of cyclodextrin-based CSP for some neutral analytes on normal phase and even exhibit better enantioseparation than the corresponding β-CD-based CSP for certain samples.
- Zhu, Lunan,Zhu, Junchen,Sun, Xiaotong,Wu, Yaling,Wang, Huiying,Cheng, Lingping,Shen, Jiawei,Ke, Yanxiong
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p. 1080 - 1090
(2020/05/25)
-
- Determination of Chemical and Enantiomeric Purity of α-Amino Acids and their Methyl Esters as N-Fluorenylmethoxycarbonyl Derivatives Using Amylose-derived Chiral Stationary Phases
-
Liquid chromatographic enantiomer separation and simultaneous determination of chemical and enantiomeric purity of α-amino acids and their methyl esters as N-fluorenylmethoxycarbonyl (FMOC) derivatives was performed on three covalently bonded type chiral stationary phases (CSPs) derived from amylose derivatives. The enantiomer separation of α-amino acid esters as N-FMOC derivatives was better than that of the corresponding acids, especially for CSP 1 and 2. Chemical impurities as the corresponding racemic acids present in several commercially available racemic amino acid methyl esters were observed to be 0.49–17.50%. Enantiomeric impurities of several commercially available L-amino acid methyl esters were found to be 0.03–0.58%, whereas chemical impurities as the corresponding racemic acids present in the same analytes were found to be 0.13–13.62%. This developed analytical method will be useful for the determination of chemical and enantiomeric purity of α-amino acids and/or esters as N-FMOC derivatives using amylose-derived CSPs.
- Islam, Md. Fokhrul,Adhikari, Suraj,Paik, Man-Jeong,Lee, Wonjae
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p. 332 - 338
(2019/04/13)
-
- Unwanted hydrolysis or α/β-peptide bond formation: How long should the rate-limiting coupling step take?
-
Nowadays, in Solid Phase Peptide Synthesis (SPPS), being either manual, automated, continuous flow or microwave-assisted, the reaction with various coupling reagents takes place via in situ active ester formation. In this study, the formation and stability of these key active esters were investigated with time-resolved 1H NMR by using the common PyBOP/DIEA and HOBt/DIC coupling reagents for both α- and β-amino acids. Parallel to the amide bond formation, the hydrolysis of the α/β-active esters, a side reaction that is a considerable efficacy limiting factor, was studied. Based on the chemical nature/constitution of the active esters, three amino acid categories were determined: (i) the rapidly hydrolyzing ones (t 24 h) in solution. The current insight into the kinetics of this key hydrolysis side reaction serves as a guide to optimize the coupling conditions of α- and β-amino acids, thereby saving time and minimizing the amounts of reagents and amino acids to be used-all key factors of more environmentally friendly chemistry.
- Goldschmidt G?z, Viktória,Nagy, Adrienn,Farkas, Viktor,Keszei, Ern?,Perczel, András
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p. 30720 - 30728
(2019/10/28)
-
- Structure-guided engineering of: Meso -diaminopimelate dehydrogenase for enantioselective reductive amination of sterically bulky 2-keto acids
-
meso-Diaminopimelate dehydrogenase (DAPDH) and mutant enzymes are an excellent choice of biocatalysts for the conversion of 2-keto acids to the corresponding d-amino acids. However, their application in the enantioselective reductive amination of bulky 2-keto acids, such as phenylglyoxylic acid, 2-oxo-4-phenylbutyric acid, and indole-3-pyruvic acid, is still challenging. In this study, the structure-guided site-saturation mutagenesis of a Symbiobacterium thermophilum DAPDH (StDAPDH) gave rise to a double-site mutant W121L/H227I, which showed dramatically improved enzyme activities towards various 2-keto acids including these sterically bulky substrates. Several d-amino acids were prepared in optically pure form. The molecular docking of substrates into the active sites of wild-type and mutant W121L/H227I enzymes revealed that the substrate binding cavity of the mutant enzyme was reshaped to accommodate these bulky substrates, thus leading to higher enzyme activity. These results lay a foundation for further shaping the substrate binding pocket and manipulating the interactions between the substrate and binding sites to access highly active d-amino acid dehydrogenases for the preparation of synthetically challenging d-amino acids.
- Cheng, Xinkuan,Chen, Xi,Feng, Jinhui,Wu, Qiaqing,Zhu, Dunming
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p. 4994 - 5002
(2018/10/17)
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- Fmoc-OPhth, the reagent of Fmoc protection
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Fmoc-OSu has been widely used for Fmoc protection of amino groups, especially amino acids, in solid phase peptide synthesis. However, it has been recognized that Fmoc-βAla-OH is formed as a by-product via the Lossen rearrangement during the reaction. Since we reconfirmed the formation of Fmoc-βAla-OH during the preparation of Fmoc-AA-OH by Fmoc-OSu, Fmoc-OPhth was designed and synthesized as a new Fmoc reagent to avoid the formation of Fmoc-βAla-OH. Furthermore, Fmoc protection by Fmoc-OPhth and Fmoc-SPPS were evaluated. The various Fmoc-amino acids prepared by Fmoc-OPhth were carried out in good yields and these are applicable in Fmoc-SPPS.
- Yoshino, Ryo,Tokairin, Yoshinori,Kikuchi, Mari,Konno, Hiroyuki
-
supporting information
p. 1600 - 1603
(2017/04/03)
-
- Caged xanthones: Potent inhibitors of global predominant MRSA USA300
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Total of 22 caged xanthones were subjected to susceptibility testing of global epidemic MRSA USA300. Natural morellic acid showed the strongest potency (MIC of 12.5 μM). However, its potent toxicity diminishes MRSA therapeutic potential. We synthetically modified natural morellic acid to yield 13 derivatives (3a-3m). Synthetically modified 3b retained strong potency in MRSA growth inhibition, yet the toxicity was 20-fold less than natural morellic acid, permitting the possibility of using caged xanthones for MRSA therapeutic.
- Chaiyakunvat, Pongkorn,Anantachoke, Natthinee,Reutrakul, Vichai,Jiarpinitnun, Chutima
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supporting information
p. 2980 - 2983
(2016/06/13)
-
- Synthesis and biological evaluation of novel FK228 analogues as potential isoform selective HDAC inhibitors
-
Novel C4- and C7-modified FK228 analogues were efficiently synthesized in a highly convergent and unified manner. This synthesis features the amide condensation of glycine-d-cysteine-containing segments with d-valine-containing segments for the direct assembly of the corresponding seco-acids, which are key precursors of macrolactones. The HDAC inhibition assay and cell-growth inhibition analysis of the synthesized analogues revealed novel aspects of their structure-activity relationship. This study demonstrated that simple modification at the C4 and C7 side chains in FK228 is effective for improving both HDAC inhibitory activity and isoform selectivity; moreover, potent and highly isoform-selective class I HDAC1 inhibitors were identified.
- Narita, Koichi,Matsuhara, Keisuke,Itoh, Jun,Akiyama, Yui,Dan, Singo,Yamori, Takao,Ito, Akihiro,Yoshida, Minoru,Katoh, Tadashi
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p. 592 - 609
(2016/07/06)
-
- A one-pot procedure for the preparation of N-9-fluorenylmethyloxycarbonyl- α-amino diazoketones from α-amino acids
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The study describes a new "one-pot" route to the synthesis of N-9-fluorenylmethyloxycarbonyl (Fmoc) α-amino diazoketones. The procedure was tested on a series of commercially available free or side-chain protected α-amino acids employed as precursors. The conversion into the title compounds was achieved by masking and activating the α-amino acids with a single reagent, namely, 9-fluorenylmethyl chloroformate (Fmoc-Cl). The resulting N-protected mixed anhydrides were reacted with diazomethane to lead to the α-amino diazoketones, which were isolated by flash column chromatography in very good to excellent overall yields. The versatility of the procedure was verified on lipophilic α-amino acids and further demonstrated by the preparation of N-Fmoc-α-amino diazoketones also from α-amino acids containing side-chain masking groups, which are orthogonal to the Fmoc one. The results confirmed that tert-butyloxycarbonyl (Boc), tert-butyl (tBu), and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf), three acid-labile protecting groups mostly adopted in the solution and solid-phase peptide synthesis, are compatible to the adopted reaction conditions. In all cases, the formation of the corresponding C-methyl ester of the starting amino acid was not observed. Moreover, the proposed method respects the chirality of the starting α-amino acids. No racemization occurred when the procedure was applied to the synthesis of the respective N-Fmoc-protected α-amino diazoketones from l-isoleucine and l-threonine and to the preparation of a diastereomeric pair of N-Fmoc-protected dipeptidyl diazoketones.
- Siciliano, Carlo,De Marco, Rosaria,Guidi, Ludovica Evelin,Spinella, Mariagiovanna,Liguori, Angelo
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p. 10575 - 10582
(2013/02/22)
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- New TFA-free cleavage and final deprotection in Fmoc solid-phase peptide synthesis: Dilute HCl in fluoro alcohol
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A novel method for cleaving from resin and removing acid-labile protecting groups for the Fmoc solid-phase peptide synthesis is described. 0.1 N HCl in hexafluoroisopropanol or trifluoroethanol cleanly and rapidly removes the tert-butyl ester and ether, Boc, trityl, and Pbf groups and cleaves the common resin linkers: Wang, HMPA, Rink amide, and PAL. Addition of just 5-10% of a hydrogen-bonding solvent considerably retards or even fully inhibits the reaction. However, a non-hydrogen-bonding solvent is tolerated.
- Palladino, Pasquale,Stetsenko, Dmitry A.
-
supporting information
p. 6346 - 6349
(2013/02/25)
-
- Benzotriazole reagents for the syntheses of Fmoc-, Boc-, and Alloc-protected amino acids
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Stable Fmoc-, Boc-, and Alloc-benzotriazoles react with various amino acids including unprotected serine and glutamic acid, in the presence of triethylamine at 20° as reagents to introduce -amino protecting groups to afford Fmoc-, Boc-, and Alloc-protected amino acids (77-94%) free of dipeptide and tripeptide impurities. Fmoc-, and Alloc-Gly-Gly-OH dipeptides were prepared in 90% yields by N-acylation of glycylglycine with Fmoc- and Alloc-benzotriazoles in the presence of triethylamine. Synthesized N-protected amino acids were greater than 99% pure, analyzed by HPLC. Georg Thieme Verlag Stuttgart - New York.
- Ibrahim, Tarek S.,Tala, Srinivasa R.,El-Feky, Said A.,Abdel-Samii, Zakaria K.,Katritzky, Alan R.
-
supporting information; experimental part
p. 2013 - 2016
(2011/10/08)
-
- Liquid-chromatography quantitative analysis of 20 amino acids after derivatization with FMOC-CI and its application to different origin Radix isatidis
-
We developed a simple, rapid and reliable method for determination of 20 common amino acids based on derivatization with 9-fluorenylmethyl chloroformate (FMOC-CI) and RP-LC/UV, this method was first introduced into quantitative analysis of amino acids. The amino groups of amino acids were trapped with FMOC-CI to form amino acid-FMOC-Cl adducts which can be suitable for LC-UV. Chromatographic separation was performed on a C18 column with a mobile phase gradient consisting of acetonitrile and sodium acetate solution. This method was shown to be sensitive for 20 common amino acids. In the intra-day precisions assay, the range of RSDs was 3.21-7.67% with accuracies of 92.34-102.51%; for the inter-day precisions assay, the range of RSDs was 5.82-9.19% with accuracies of 90.25-100.63%. The results also indicated that solutions of amino acids-FMOC-Cl can be kept at room temperature for at least 24 h without showing significant losses in the quantified values. The validated method was successfully applied to the determination of major four kinds of amino acids in R. isatidis samples (Arg, Pro, Met and Val). The total content of amino acids in different origin R. isatidis was 13.32-19.16 mg/g. The differences between R. isatidis samples were large using HCA.
- Zhou, Wei,Zhang, Xiao-Yan,Duan, Geng-Li
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experimental part
p. 509 - 515
(2012/01/04)
-
- BENZYLIC COMPOUND
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The present invention provides a protecting reagent that can be removed in a high yield even under acidic conditions and can afford a resulting product at a high purity in an organic synthesis reaction such as peptide synthesis and the like. The inventive protecting reagent is particular benzylic compound having only one hydroxyl group substituted by an organic group having an aliphatic hydrocarbon group having a carbon number of not less than 14.
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- Poly(vinyl)chloride supported palladium nanoparticles: Catalyst for rapid hydrogenation reactions
-
Palladium nanoparticles supported over poly(vinyl)chloride matrix (PVC-Pd0) are prepared through an efficient and inexpensive protocol. The catalyst has been characterized by XRD, SEM and TEM and its utility for the reduction of a range of functional groups as well as for the removal of some common protecting groups employed in peptide chemistry is demonstrated.
- Hemantha, Hosahalli P.,Sureshbabu, Vommina V.
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experimental part
p. 2597 - 2601
(2011/05/12)
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- Reversible hydrogen transfer between cysteine thiyl radical and glycine and alanine in model peptides: Covalent H/D exchange, radical-radical reactions, and l - To D -Ala conversion
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The reversible intramolecular hydrogen transfer reaction of peptide Cys thiyl radicals with Gly and Ala residues was studied in model peptides, where thiyl radicals were either generated through photochemical cleavage of disulfide bonds or through the rea
- Mozziconacci, Olivier,Kerwin, Bruce A.,Sch?neich, Christian
-
experimental part
p. 6751 - 6762
(2011/01/03)
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- Derivates of Polyethylene Glycol Modified Thymosin Alpha 1
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Pharmaceutical compositions that include thymosin alpha 1 peptide derivatives modified at the C-terminal of the peptide chain with polyethylene glycol, and their pharmaceutical acceptable salts, are generally disclosed. Also, new methods used to prepare these thymosin alpha 1 peptide derivatives modified at the C-terminal of the peptide chain with polyethylene glycol are generally provided. The presently disclosed compounds and their salts can be prepared administered to humans to treat immune disease and can also be used in adjuvant treatment.
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- Efficient procedure for the preparation of oligomer-free N-fmoc amino acids
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A two-step method is presented for the peptide-free, high-purity, and high-yield synthesis of N-Fmoc amino acids. The first step involves the preparation of stable dicyclohexylammonium-amino acid ionic adduct in acetone. Subsequently, the ionic adducts, on reaction with Fmoc-Nosu under mild alkaline conditions, give dipeptide-free N-Fmoc amino acids. The positive charge of the dicyclohexylammonium counterion in the ionic salt has a longer radius, moderating the nucleophilicity of the carboxylate ion of the amino acid and preventing by-products by arresting the formation of mixed anhydrides, the precursors of oligopeptide impurities.
- Nowshuddin, Shaik,Rao,Reddy, A. Ram
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experimental part
p. 2022 - 2031
(2009/11/30)
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- Synthesis of A83586C analogs with potent anticancer and β-catenin/TCF4/osteopontin inhibitory effects and insights into how A83586C modulates E2Fs and pRb
-
(Chemical Equation Presented) The synthesis of three potent new antitumor agents is described: the A83586C -citropeptin hybrid (1), the A83586C-GE3 hybrid (2), and L-Pro-A83586C (3). Significantly, compounds 1 and 2 function as highly potent inhibitors of β-catenin/TCF4 signaling within cancer cells, while simultaneously downregulating osteopontin (Opn) expression. A83586C antitumor cyclodepsipeptides also inhibit E2F-mediated transcription by downregulating E2F1 expression and inducing dephosphorylation of the oncogenic hyperphosphorylated retinoblastoma protein (pRb).
- Hale, Karl J.,Manaviazar, Soraya,Lazarides, Linos,George, Jonathan,Walters, Marcus A.,Cai, Jiaqiang,Delisser, Vern M.,Bhatia, Gurpreet S.,Peak, S. Andrew,Dalby, Stephen M.,Lefranc, Amandine,Chen, Ying-Nan P.,Wood, Alexander W.,Crowe, Paul,Erwin, Pauline,El-Tanani, Mohamed
-
supporting information; experimental part
p. 737 - 740
(2009/09/27)
-
- A nonacid degradable linker for solid-phase synthesis
-
Synthesis and applications of two new nonacid degradable linkers as an alternative to the Wang linker for solid-phase synthesis are described. Resin from linker 2 looks superior to linker 1 in terms of yields for both anchoring of the first building block and cleavage and in terms of higher purity of the final product. Use of linker 2 avoids side reactions associated with the use of Wang resin due to an undesired cleavage during final acid treatment.
- Colombo, Aina,De La Figuera, Natalia,Fernandez, Joan Carles,Fernandez-Forner, Dolors,Albericio, Fernando,Forns, Pilar
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p. 4319 - 4322
(2008/03/11)
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- Pd-C-induced catalytic transfer hydrogenation with triethylsilane
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(Chemical Equation Presented) In situ generation of molecular hydrogen by addition of triethylsilane to palladium-charcoal catalyst results in rapid and efficient reduction of multiple bonds, azides, imines, and nitro groups, as well as benzyl group and allyl group deprotection under mild, neutral conditions.
- Mandal, Pijus K.,McMurray, John S.
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p. 6599 - 6601
(2008/02/10)
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- Amphiphilic cyclodextrin derivatives, method for preparation thereof and uses thereof
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The invention relates to cyclodextrin derivatives of formula (I): in which: R1═—NH-E-AA-(L1)p(L2)q where E=a linear or branched Cl-Cl5 hydrocarbon-based group with, optionally, one or more hetero atoms; AA=the residue of an amino acid; L1 and L2=a C6-C24 hydrocarbon-based group with, optionally, one or more hetero atoms; p and q=0 or 1, at least one being ≠0; R2═H, —CH3, isopropyl, hydroxypropyl, sulphobutyl ether; R3═H or R2, except when R2=hydroxypropyl; all the R4═—OH or R2, except when R2=hydroxypropyl, or at least one of the R4═R1; n=5, 6 or 7. The invention also relates to a process for preparing them, and to inclusion complexes and organized surfactant systems comprising them.
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Page/Page column 24
(2010/11/27)
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- Enzyme-cleavable linkers for peptide and glycopeptide synthesis
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Hydroxymethylphenoxy linkers that are commonly used in solid phase peptide synthesis are surprisingly susceptible to efficient cleavage by the protease chymotrypsin with a broad range of amino acid residues being tolerated at the scissile bond; this enzyme-cleavable linker system has been applied to peptide and glycopeptide synthesis. The Royal Society of Chemistry 2005.
- Maltman, Beatrice A.,Bejugam, Mallesham,Flitsch, Sabine L.
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p. 2505 - 2507
(2007/10/03)
-
- Antiangiogenic peptides
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Mammalian kringle 5 fragments and kringle 5 fusion proteins are disclosed as a compounds for treating angiogenic diseases. Methods and compositions for inhibiting angiogenic diseases are also disclosed.
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- Resin for solid phase synthesis
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A crosslinked polymer bead which, when: (i) functionalized with a 2-chlorotrityl chloride group; (ii) coupled with Leu to 0.65 mmol/g; and (iii) coupled with Glu(t-Bu); allows coupling of FMOC-Lys(BOC)-OH at an amount of 1.5 equivalents in the presence of 1.5 equivalents of HOBT, 1.5 equivalents of DIEA and 1.5 equivalents of HBTU, to be completed, as determined by the Kaiser test, in no more than 35 minutes.
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-
- Treatment of obesity
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A method for the treatment of obesity in an animal such as a human, comprises administering to the animal an effective amount of a peptide which comprises an analogue of the carboxyl-terminal sequence of a growth hormone, particularly an analogue of the carboxyl-terminal sequence of human growth hormone containing amino acid residues 177-191. A pharmaceutical composition for use in the treatment of obesity is also disclosed.
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- GLP-2 compounds, formulations, and uses thereof
-
The present invention relates to novel human glucagon-like peptide-2 (GLP-2) peptides and human glucagon-like peptide-2 derivatives which have a protracted profile of action as well as polynucleotide constructs encoding such peptides, vectors and host cells comprising and expressing the polynucleotide, pharmaceutical compositions, uses and methods of treatment.
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-
- A new polymer-supported reagent for the Fmoc-protection of amino acids
-
A new polymer-supported Fmoc-OSu (Fmoc-P-OSu) has been prepared from polymer-bound N-hydroxysuccinimide (P-HOSu), and used as a solid-supported reagent for the Fmoc-protection of amino groups. The residual P-HOSu generated after the protection reaction can be separated by simple filtration and reused.
- Chinchilla, Rafael,Dodsworth, David,Nájera, Carmen,Soriano, José
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p. 7579 - 7581
(2007/10/03)
-
- CYCLIC DEPSIPEPTIDES AND DRUGS CONTAINING THE SAME AS THE ACTIVE INGREDIENT
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Cyclic depsipeptides represented by the formula (1) (wherein: R is a straight or branched alkyl group of 5-20 carbon atoms or a straight or branched alkoxymethyl group of 5-15 carbon atoms; A, B, D, E and F independently each other are alanine, valine, leucine, isoleucine, phenylalanine, etc.; W and Z independently each other are aspartic acid, asparagine, glutamic acid or glutamine; and m and n independently each other is 0 or 1) or pharmacologically acceptable salts thereof. The present compounds are prepared according to a method conventionally used in peptide synthesis. The present compounds are useful as an agent for promoting the production of apolipoprotein E, a therapeutic agent for neurologic damages, a therapeutic agent for dementia, an agent for inhibiting the production of apolipoprotein B, an agent for promoting the production of apolipoprotein A1 or a therapeutic agent for hyperlipemia.
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-
- Apparatus and methods for detecting antibodies
-
A single, unitary, solid phase support apparatus having a planar surface divided into a plurality of separate zone functions to detect antibodies. Each zone has bonded to it, a different peptide through its C-terminal end. The zones are incubated with the analyte sample and observed for reaction, indicating the virus-specific or bacteria specific presence or absence.
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-
- Highly practical methodology for the synthesis of D- and L-α-amino acids, N-protected α-amino acids, and N-methyl-α-amino acids
-
Full details are provided for an exceedingly practical method to synthesize D- and L-α-amino acids, N-protected α-amino acids, and N-methyl-α-amino acids, employing as a key step the asymmetric alkylation of pseudoephedrine glycinamide (1) or pseudoephedrine sarcosinamide (2). Practical procedures for the synthesis of 1 and 2 from pseudoephedrine and glycine methyl ester or sarcosine methyl ester, respectively, are presented. Optimum protocols for the enolization and subsequent alkylation of 1 and 2 are described. Alkylation reactions of 1 and 2 are found to be quite efficient with a wide range of alkyl halide substrates, and the products are formed with high diastereoselectivity. The products of these alkylation reactions are hydrolyzed efficiently and with little to no racemization simply by heating in water or water-dioxane mixtures. This protocol provides an exceedingly practical method for the preparation of salt-free α-amino acids of high enantiomeric purity. Alternatively, the alkylation products may be hydrolyzed in high yield and with little to no racemization by heating with aqueous sodium hydroxide. The alkaline hydrolyzate can then be treated with an acylating reagent to provide directly highly enantiomerically enriched N-protected derivatives such as N-Boc and N-Fmoc. Key features necessary for the successful execution of these experimental procedures are identified.
- Myers, Andrew G.,Gleason, James L.,Yoon, Taeyoung,Kung, Daniel W.
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p. 656 - 673
(2007/10/03)
-
- Potential formation of intramolecular inclusion complexes in peptidocyclodextrins as evidenced by NMR spectroscopy
-
Investigations of the structure of β- and γ-cyclodextrin derivatives in solution obtained by grafting amino acids or peptides are presented.These compounds are models for vectorization-dedicated molecular carriers.It is shown that for some amino acids, strong intramolecular self-inclusion complexes are formed in aqueous solution.This process strongly depends upon the nature and position of the pertinent amino acid in the peptide sequence.Two dimensional NMR experiments are used in conjunction with competition with external guests to evidence and estimate the strength of these auto-inclusion complexes.
- Djedaini-Pilard, Florence,Azaroual-Bellanger, Nathalie,Gosnat, Muriel,Vernet, Delphine,Perly, Bruno
-
p. 723 - 730
(2007/10/02)
-
- Method for treating inflammation and compounds and compositions suitable for use therein
-
The present invention relates to a method of treating an inflammatory condition, and to compounds and composition suitable for use in such a method, which compounds have the Formula: STR1 wherein: X is methylene, ethylene, ethyleneoxy, or oxygen; Q is STR2 where C' is a residue of a lipophilic amino acid, and Y is --CO2 H, --CH2 OH, --CONR1 R2, or --CO2 R1 where R1 and R2 hydrogen, alkyl, or aryl; R3 and R4 are, independently, hydrogen, alkyl or aryl; and A and B are, independently, hydrogen, fused phenyl, alkyl, aryl, alkaryl, aralkyl, alkoxy, alkoxyalkyl, halogen, or nitro; or pharmaceutically acceptable salts thereof.
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-
- Non-destructive Cleavage of N-Acylsultams Under Neutral Conditions: Preparation of Enantiomerically, Pure Fmoc-Protected α-Amino Acids
-
Heating diastereoisomerically pure N-acylsultams 3 or 4 with allyl alcohol/Ti(OR)4 efficiently yields sultams 1 or 2 and allyl esters 5.Esters 5 are hydrolyzed under nonbasic conditions in the presence of Wilkinson's catalyst to give enantiomerically and diastereoisomerically pure carboxylic acids 7.A series of carbonyl-(Fmoc)-protected amino acids 14 were thus prepared from N-acylsultams 12.
- Oppolzer, Wolfgang,Lienard, Philippe
-
p. 2572 - 2582
(2007/10/02)
-
- A New Synthesis of Thymosin α1
-
Thymosin α1, an N-acetylated octacosa thymus peptide, isolated first from thymosin fraction 5, is synthesized by the solid phase method using the p-benzyloxybenzyl alcohol/polystyrene/divinylbenzene resin, Nα-Fmoc-amino acids and those with tert-butyl or Boc side chain protection.All couplings are performed with the Bop reagent.The peptide is purified by a combination of gel chromatography and preparative HPLC, its purity checked by amino acid analysis and analytical HPLC, and the biological activity tested by the E-rosette assay.
- Echner, Hartmut,Voelter, Wolfgang
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p. 1095 - 1098
(2007/10/02)
-
- 9-Fluorenylmethyl Pentafluorophenyl Carbonate as a Useful Reagent for the Preparation of N-9-Fluorenylmethyloxycarbonylamino Acids and their Pentafluorophenyl Esters
-
9-Fluorenylmethyl pentafluorophenyl carbonate is a useful reagent for the efficient, side reaction-free introduction of N-9-fluorenylmethyloxycarbonyl protecting group into amino acids and for the subsequent preparation of their pentafluorophenyl esters.Some new compounds of both types are described.
- Schoen, Istvan,Kisfaludy, Lajos
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p. 303 - 305
(2007/10/02)
-
- Solid phase synthesis without repetitive acidolysis. Preparation of leucyl-alanyl-glycyl-valine using 9-fluorenylmethyloxycarbonylamino acids.
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The utility of repetitive nonhydrolytic base cleavage of alpha-amino protective groups in solid phase peptide synthesis is shown by a preparation of the model tetrapeptide leucyl-alanyl-glycyl-valine on a p-benzyloxybenzyl ester polystyrene--1% divinylbenzene resin support. Nalpha-9-Fluorenylmethyloxycarbonyl (Fmoc: Carpino & Han, 1970, 1972) amino acids were coupled by the symmetrical anhydride procedure, followed by Fmoc group cleavage using 50% piperidine in methylene chloride. Quantitative removal of the Fmoc-tetrapeptide from the solid support was effected by treatment with 55% trifluoroacetic acid in methylene chloride. Homogeneous free tetrapeptide was obtained in 87% overall yield. The procedure is proposed to offer advantages over present solid phase methods which use acidolysis for repetitive alpha-amino group deblocking.
- Meienhofer,Waki,Heimer,Lambros,Makofske,Chang
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p. 35 - 42,37,39
(2007/10/06)
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- Pyroglutamyl-histidyl-tryptophanyl-seryl-tyrosyl hydrazides
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A new decapeptide having the formula, pGlu-His-Trp-Ser-Tyr-Gly-Leu-NO2 Arg-Pro-Gly(NH2); salts thereof; production thereof by reacting pGlu-His-Trp-Ser-Tyr(N3) with Gly-Leu-NO2 Arg-Pro-Gly(NH2), by reacting pGlu-His-Trp-Ser-Tyr-Gly(N3) with Leu-NO2 Arg-Pro-Gly(NH2), or by reacting pGlu-His-Trp-Ser-Tyr-Gly-Leu(N3) with NO2 Arg-Pro-Gly(NH2); certain peptide intermediates and their salts used in the production thereof; and the use thereof in the preparation of luteinizing hormone releasing factor.
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- Solid phase synthesis with base N alpha-protecting group cleavage
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An improved solid phase peptide synthesis method is disclosed utilizing base labile Nα-amino acid protecting groups. Such method provides a more efficient synthesis procedure in that it eliminates acid treatment thereby preventing loss of peptide from the support during each deprotection cycle and eliminates a substantial number of wash cycles in each step. A preferred base labile Nα-amino protecting group is the 9-fluorenylmethyloxycarbonyl group (Fmoc) and a preferred base for deprotection is piperidine.
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