- An efficient peptide ligation using azido-protected peptides via the thioester method
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Azido-protected Fmoc-Lys-OH (Fmoc-Lys(N3)-OH) was synthesized from Fmoc-Lys-OH by the copper(II)-catalyzed diazo transfer method, and introduced to a peptide by the ordinary Fmoc-based solid-phase peptide synthesis. This azido peptide could be condensed with a peptide thioester by the Ag+-free thioester method without any significant side reactions. The azido group was easily reduced to an amino group by Zn powder after peptide condensation.
- Katayama, Hidekazu,Hojo, Hironobu,Ohira, Tsuyoshi,Nakahara, Yoshiaki
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- Click chemistry as a macrocyclization tool in the solid-phase synthesis of small cyclic peptides
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Despite the vast number of techniques developed for the cyclization of small peptides, cyclization efficiency remains problematic in peptides that lack turn-promoting structures. Here we demonstrate the utility of click chemistry as a macrocyclization tool in the solid-phase synthesis of cyclic tetra-, penta-, hexa-, and heptapeptides. On-resin cyclization is completed at room temperature within 6 h, resulting in predominantly monomer with small amounts of cyclomultimer byproducts.
- Turner, Rushia A.,Oliver, Allen G.,Lokey, R. Scott
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- Site-directed spin-labeling of nucleic acids by click chemistry: Detection of abasic sites in duplex DNA by EPR spectroscopy
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This paper describes a spin label that can detect and identify local structural deformations in duplex DNA, in particular abasic sites. The spin label was incorporated into DNA by a new postsynthetic approach using click-chemistry on a solid support, which simplified both the synthesis and purification of the spin-labeled oligonucleotides. A nitroxide-functionalized azide, prepared by a short synthetic route, was reacted with an oligomer containing 5-ethynyl-2′-dU. The conjugation proceeded in quantitative yield and resulted in a fairly rigid linker between the modified nucleotide and the nitroxide spin label. The spin label was used to detect, for the first time, abasic sites in duplex DNA by X-band CW-EPR spectroscopy and give information about other structural deformations as well as local conformational changes in DNA. For example, reduced mobility of the spin label in a mismatched pair with T was consistent with the spin label displacing the T from the duplex. Addition of mercury(II) to this mispair resulted in a substantial increase in the motion of the spin label, consistent with formation of a metallopair between the T and the spin-labeled base that results in movement of the spin label out of the duplex and toward the solution. Thus, reposition of the spin label, when acting as a mercury(II)-controlled mechanical lever, can be readily detected by EPR spectroscopy. The ease of incorporation and properties of the new spin label make it attractive for EPR studies of nucleic acids and other macromolecules.
- Jakobsen, Ulla,Shelke, Sandip A.,Vogel, Stefan,Sigurdsson, Snorri Th.
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- Iterative in situ click chemistry assembles a branched capture agent and allosteric inhibitor for akt1
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We describe the use of iterative in situ click chemistry to design an Akt-specific branched peptide triligand that is a drop-in replacement for monoclonal antibodies in multiple biochemical assays. Each peptide module in the branched structure makes unique contributions to affinity and/or specificity resulting in a 200 nM affinity ligand that efficiently immunoprecipitates Akt from cancer cell lysates and labels Akt in fixed cells. Our use of a small molecule to preinhibit Akt prior to screening resulted in low micromolar inhibitory potency and an allosteric mode of inhibition, which is evidenced through a series of competitive enzyme kinetic assays. To demonstrate the efficiency and selectivity of the protein-templated in situ click reaction, we developed a novel QPCR-based methodology that enabled a quantitative assessment of its yield. These results point to the potential for iterative in situ click chemistry to generate potent, synthetically accessible antibody replacements with novel inhibitory properties.
- Millward, Steven W.,Henning, Ryan K.,Kwong, Gabriel A.,Pitram, Suresh,Agnew, Heather D.,Deyle, Kaycie M.,Nag, Arundhati,Hein, Jason,Lee, Su Seong,Lim, Jaehong,Pfeilsticker, Jessica A.,Sharpless, K. Barry,Heath, James R.
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- A general and efficient cobalt(II)-based catalytic system for highly stereoselective cyclopropanation of alkenes with α-cyanodiazoacetates
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[Co(P1)], the cobalt(II) complex of the D2-symmetric chiral porphyrin 3,5-DitBu-ChenPhyrin, is an effective catalyst for catalyzing asymmetric olefin cyclopropanation with the acceptor/acceptor-type diazo reagent α-cyanodiazoacetates
- Zhu, Shifa,Xu, Xue,Perman, Jason A.,Zhang, X. Peter
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- Simultaneous and site-directed incorporation of an ester linkage and an azide group into a polypeptide by in vitro translation
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A method is presented by which an azide-containing side chain can be introduced into any internal position of a polypeptide chain by in vitro translation. For this, 2′-deoxy-cytidylyl-(3′→5′)- adenosine was acylated on the 3′(2′)-hydroxyl group of adenosine with 6-azido-2(S)-hydroxyhexanoic acid (AHHA), an α-hydroxy- and ε-azide derivative of l-lysine. The acylated dinucleotide was enzymatically ligated with a tRNA transcript to provide chemically stable E. coli suppressor AHHA-tRNACys(CUA). The esterase 2 gene from Alicyclobacillus acidocaldarius was modified by the amber stop codon (UAG) on position 118. Using AHHA-tRNACys(CUA) in an E. coli in vitro translation/transcription system, the site-directed introduction of an azide group linked to a backbone ester into the esterase polypeptide was achieved. The yield of the synthesized modified protein reached 80% compared to translation of the native esterase. Subsequently, azide coupling with an alkyne-modified oligodeoxynucleotide demonstrated the feasibility of this approach for conjugation of polypeptides.
- Humenik, Martin,Huang, Yiwei,Safronov, Igor,Sprinzl, Mathias
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- Anomeric effects in sulfonyl compounds: An experimental and computational study of fluorosulfonyl azide, FSO2N3, and trifluoromethylsulfonyl azide, CF3SO2N3
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Fluorosulfonyl azide, FSO2N3, was characterized by IR (gas phase, Ar matrix), and Raman (liquid) spectroscopy. According to the matrix IR spectrum of 18O-labeled FSO2N3, its two oxygen atoms are nonequivalent. This assumption was confirmed by the X-ray crystal structure of FSO2N3 at -123 °C, as only one conformer was observed with one of the S - O bonds in synperiplanar position to the N3 group (φ(OS-NN) = -14.8(3)°) with respect to the S-N bond. The same conformation was found for trifluoromethylsulfonyl azide, CF 3SO2N3 (φ(OS-NN) = -23.74(15)°), in the solid state. The preference of such a synperiplanar configuration between S - O and N3 was rationalized by a predominant anomeric interaction of nω(N) → ω * (S-O), as supported by the experiment and quantum chemical calculations.
- Zeng, Xiaoqing,Gerken, Michael,Beckers, Helmut,Willner, Helge
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- Functional Assemblies Emerging in Complex Mixtures of Peptides and Nucleic Acid–Peptide Chimeras
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Striking synergy between nucleic acids and proteins is exhibited in living cells. Whether such mutual activity can be performed using simple supramolecular nucleic acid–peptide (NA-pep) architectures remains a mystery. To shed light on this question, we studied the emergence of a primitive synergy in assemblies of short DNA-peptide chimeras. Specifically, we characterized multiple structures forming along gradual mixing trajectory, in which a peptide solution was seeded with increasing amounts of NA-pep chimeras. We report on the systematic change from β-sheet-peptide-based fibrillar architectures into the spherical structures formed by the conjugates. Remarkably, we find that through forming onion-like structures, the conjugates exhibit increased DNA hybridization stability and bind small molecules more efficiently than the peptides or DNA alone. A brief discussion highlights the implications of our findings for the production of new materials and for research on the origin of life.
- Chotera, Agata,Sadihov, Hava,Cohen-Luria, Rivka,Monnard, Pierre-Alain,Ashkenasy, Gonen
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- Spectroscopic studies of trifluoromethanesulfonyl azide, CF3SO2N3
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The FTIR spectra of the vapour and the Raman spectra of the liquid were obtained for trifluoromethanesulfonyl azide, CF3SO2N3. Vibrational assignments were made for all fundamentals but one of the torsional vibrations, the SO2 rocking mode, and the two CF3 deformations. A subsequent normal coordinate analysis was performed. The observed features and the evaluation of the band contours appearing in the FTIR spectrum of the vapour can be interpreted in terms of the existence of only one conformation belonging to the C1 symmetry point group. This was also deduced from preliminary results of a gas electron diffraction analysis. Theoretical calculations (HF/6-31G*, MP2/6-31G*, BPW91/6-31G*, B3PW91/6-31G* and B3PW91/6-311 + G*) were performed both in order to study the conformational properties of CF3SO2N3 and in order to calculate the vibrational frequencies.
- Alvarez,Cutin,Romano,Mack,Della Vedova
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- The synthesis of androstane brassinosteroid analogues with α-azido acid ester groups in position 17β
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Androstane brassinosteroid analogues with α-azido acid ester groups in position 17β were synthesized from 2α,3α,17β- trihydroxy-5α-androstan-6-one after the protection of the 2α,3α-diols upon treatment with the corresponding α-azido acid and the subsequent deprotection of the diol grouping. Six new castasterone analogues were prepared. The biological activities were evaluated in two bioassays: a rice lamina inclination test and bean second internode bioassays. The activities of the new analogues differ in these two bioassays.
- Hnilickova, Jaroslava,Kohout, Ladislav,Capdevila, Enric,Esteve, Ana,Vilaplana, Marc,Molist, Meritxell,Brosa, Carme,Swaczynova-Oklestkova, Jana,Slavikova, Barbora
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- Rhodium(II) carbene-mediated modification of 2-deoxystreptamine surrogates
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Rhodium(II)-catalyzed decomposition of carbene precursors grafted to the alcohol of diaminocyclopentanols promotes clean formation of a C-N bond via 1,6-insertion into an adjacent carbamate or azide. These modifications of 2-deoxystreptamine surrogates mi
- Blond, Aurélie,Moumné, Roba,Bégis, Guillaume,Pasco, Morgane,Lecourt, Thomas,Micouin, Laurent
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- Octakis(3-azidopropyl)octasilsesquioxane: A versatile nanobuilding block for the efficient preparation of highly functionalized cube-octameric polyhedral oligosilsesquioxane frameworks through click assembly
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A one-step synthesis of octa-kis(3-azidopropyl)octasilsesquioxane from commercially available octakis(3-aminopropyl)octasilsesquioxane has been developed through a highly effi-cient diazo-transfer reaction under very mild conditions. Nonaflyl azide is sho
- Trastoy, Beatriz,Eugenia Perez-Ojeda,Sastre, Roberto,Chiara, Jose Luis
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- Clickable functionalization of liposomes with the gH625 peptide from herpes simplex virus type i for intracellular drug delivery
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Liposomes externally modified with the nineteen residues gH625 peptide, previously identified as a membrane-perturbing domain in the gH glycoprotein of Herpes simplex virus type I, have been prepared in order to improve the intracellular uptake of an enca
- Tarallo, Rossella,Accardo, Antonella,Falanga, Annarita,Guarnieri, Daniela,Vitiello, Giuseppe,Netti, Paolo,D'Errico, Gerardino,Morelli, Giancarlo,Galdiero, Stefania
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- Oxa-adamantyl cannabinoids
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As a continuation of earlier work on classical cannabinoids bearing bulky side chains we report here the design, synthesis, and biological evaluation of 3′-functionalized oxa-adamantyl cannabinoids as a novel class of cannabinergic ligands. Key synthetic steps involve nucleophilic addition/transannular cyclization of aryllithium to epoxyketone in the presence of cerium chloride and stereoselective construction of the tricyclic cannabinoid nucleus. The synthesis of the oxa-adamantyl cannabinoids is convenient, and amenable to scale up allowing the preparation of these analogs in sufficient quantities for detailed in vitro evaluation. The novel oxa-adamantyl cannabinoids reported here were found to be high affinity ligands for the CB1 and CB2 cannabinoid receptors. In the cyclase assay these compounds were found to behave as potent and efficacious CB1 receptor agonists. Isothiocyanate analog AM10504 is capable of irreversibly labeling both the CB1 and CB2 receptors.
- Ho, Thanh C.,Tius, Marcus A.,Nikas, Spyros P.,Tran, Ngan K.,Tong, Fei,Zhou, Han,Zvonok, Nikolai,Makriyannis, Alexandros
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supporting information
(2021/03/14)
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- Synthesis of diversely functionalised 2,2-disubstituted oxetanes: Fragment motifs in new chemical space
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Di-, tri- and tetra-substituted oxetane derivatives with combinations of ester, amide, nitrile, aryl, sulfone and phosphonate substituents are prepared as fragments or building blocks for drug discovery. The synthesis of these novel oxetane functional groups, in new chemical space, is achieved via rhodium-catalysed O-H insertion and C-C bond forming cyclisation.
- Davis, Owen A.,Croft, Rosemary A.,Bull, James A.
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supporting information
p. 15446 - 15449
(2015/10/20)
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- QUATERNARY ALKYL AMMONIUM BACTERIAL EFFLUX PUMP INHIBITORS AND THERAPEUTIC USES THEREOF
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Disclosed are compounds having at least one quaternary alkyl ammonium functionality. The compounds inhibit bacterial efflux pump inhibitors and are used in combination with an anti-bacterial agent to treat or prevent bacterial infections. These combinations can be effective against bacterial infections that have developed resistance to anti-bacterial agents through an efflux pump mechanism.
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- One-pot synthesis of 2,4-disubstituted thiazoline from β-azido disulfide and carboxylic acid
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A concise and efficient one-pot four-step synthesis of 2,4-disubstituted thiazoline via a cascade disulfide bond cleavage/thiocarbonylation/Staudinger reduction/aza-Wittig reaction is established. Treatment of various carboxylic acids with β-azido disulfides under this one-pot procedure obtained the desired thiazolines in good to excellent isolated yields.
- Liu, Yi,Liu, Jun,Qi, Xiangbing,Du, Yuguo
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experimental part
p. 7108 - 7113
(2012/10/07)
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- Design, synthesis and the effect of 1,2,3-triazole sialylmimetic neoglycoconjugates on Trypanosoma cruzi and its cell surface trans-sialidase
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This work describes the synthesis of a series of sialylmimetic neoglycoconjugates represented by 1,4-disubstituted 1,2,3-triazole-sialic acid derivatives containing galactose modified at either C-1 or C-6 positions, glucose or gulose at C-3 position, and by the amino acid derivative 1,2,3-triazole fused threonine-3-O-galactose as potential TcTS inhibitors and anti-trypanosomal agents. This series was obtained by Cu(I)-catalysed azide-alkyne cycloaddition reaction ('click chemistry') between the azido-functionalized sugars 1-N3-Gal (commercial), 6-N 3-Gal, 3-N3-Glc and 3-N3-Gul with the corresponding alkyne-based 2-propynyl-sialic acid, as well as by click chemistry reaction between the amino acid N3-ThrOBn with 3-O-propynyl-GalOMe. The 1,2,3-triazole linked sialic acid-6-O-galactose and the sialic acid-galactopyranoside showed high Trypanosoma cruzi trans-sialidase (TcTS) inhibitory activity at 1.0 mM (approx. 90%), whilst only the former displayed relevant trypanocidal activity (IC50 260 μM). These results highlight the 1,2,3-triazole linked sialic acid-6-O-galactose as a prototype for further design of new neoglycoconjugates against Chagas' disease.
- Campo, Vanessa L.,Sesti-Costa, Renata,Carneiro, Zumira A.,Silva, Jo?o S.,Schenkman, Sergio,Carvalho, Ivone
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experimental part
p. 145 - 156
(2012/02/15)
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- Synthesis and conformational analysis of efrapeptins
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The efrapeptin family of peptide antibiotics produced by the fungus Tolypocladium niveum, and the neo-efrapeptins from the fungus Geotrichum candidumare inhibitors of F1-ATPase with promising antitumor, antimalaria, and insecticidal activity. They are rich in Cα- dialkyl amino acids (Aib, Iva, Acc) and contain one β-alanine and several pipecolic acid residues. The C-terminus bears an unusual heterocyclic cationic cap. The efrapeptins C-G and three analogues of efrapeptin C were synthesized using α-azido carboxylic acids as masked amino acid derivatives. All compounds display inhibitory activity toward F1-ATPase. The conformation in solution of the peptides was investigated with electronic CD spectroscopy, FT-IR spectroscopy, and VCD spectroscopy. All efrapeptins and most efrapeptin analogues were shown to adopt helical conformations in solution. In the case of efrapeptin C, VCD spectra proved that a 310-helix prevails. In addition, efrapeptin C was conformationally studied in detail with NMR and molecular modeling. Besides NOE distance restraints, residual dipolar couplings (RDC) observed upon partial alignment with stretched PDMS gels were used for the conformational analysis and confirmed the 310-helical conformation. Copyright
- Weigelt, Sven,Huber, Thomas,Hofmann, Frank,Jost, Micha,Ritzefeld, Markus,Luy, Burkhard,Freudenberger, Christoph,Majer, Zsuzsanna,Vass, Elemer,Greie, Joerg-Christian,Panella, Lavinia,Kaptein, Bernard,Broxterman, Quirinus B.,Kessler, Horst,Altendorf, Karlheinz,Hollosi, Miklos,Sewald, Norbert
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supporting information; experimental part
p. 478 - 487
(2012/03/08)
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- New rhodamine nitroxide based fluorescent probes for intracellular hydroxyl radical identification in living cells
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The synthesis, characteristics, and biological applications of a series of new rhodamine nitroxide fluorescent probes that enable imaging of hydroxyl radicals (?OH) in living cells are described. These probes are highly selective for ?OH in aqueous solution, avoiding interference from other reactive oxygen species (ROS), and they facilitate ?OH imaging in biologically active samples. The robust nature of these probes (high specificity and selectivity, and facile synthesis) offer distinct advantages over previous methods for ?OH detection.
- Yapici, Nazmiye B.,Jockusch, Steffen,Moscatelli, Alberto,Mandalapu, Srinivas Rao,Itagaki, Yasuhiro,Bates, Dallas K.,Wiseman, Sherri,Gibson, K. Michael,Turro, Nicholas J.,Bi, Lanrong
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supporting information; experimental part
p. 50 - 53
(2012/03/11)
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- Catalytic Cyclopropanation of Alkenes with Alpha-Cyano-Diazoacetates
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A process for the preparation of a 1,1-cyclopropane(nitrile)(electron-acceptor), the process comprising treating an olefin with an acceptor/acceptor-substituted α-cyanodiazo reagent in the presence of a catalytic amount of a metal porphyrin catalyst.
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Page/Page column 17
(2012/03/10)
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- Synthesis and cytotoxicity of ring C-Functionalized derivatives of the marine natural product (-)-dibromophakellstatin
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A structure-activity relationship study of ring C-functionalized derivatives of the cytotoxic marine natural product(-)-dibromophakellstatin from the sponge Phakellia mauritiana is reported. Functionalization of the pyrrolidine ring was achieved starting
- Moldovan, Rares-Petru,Zoellinger, Michael,Jones, Peter G.,Kelter, Gerhard,Fiebig, Heinz-Herbert,Lindel, Thomas
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experimental part
p. 685 - 698
(2012/03/27)
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- An asymmetric synthesis of l -pyrrolysine
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An efficient asymmetric synthesis of the 22nd amino acid l-pyrrolysine has been accomplished. The key stereogenic centers were installed by an asymmetric conjugate addition reaction. A Staudinger/aza-Wittig cyclization was used to form the acid-sensitive
- Wong, Margaret L.,Guzei, Ilia A.,Kiessling, Laura L.
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supporting information; experimental part
p. 1378 - 1381
(2012/05/04)
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- New β-strand templates constrained by Huisgen cycloaddition
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New peptidic templates constrained into a β-strand geometry by linking acetylene and azide containing P1 and P3 residues of a tripeptide by Huisgen cycloaddition are presented. The conformations of the macrocycles are defined by NMR studies and those that best define a β-strand are shown to be potent inhibitors of the protease calpain. The β-strand templates presented and defined here are prepared under optimized conditions that should be suitable for targeting a range of proteases and other applications requiring such a geometry.
- Pehere, Ashok D.,Abell, Andrew D.
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supporting information; experimental part
p. 1330 - 1333
(2012/05/20)
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- Discovery and extensive in vitro evaluations of NK-HDAC-1: A chiral histone deacetylase inhibitor as a promising lead
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Herein, further SAR studies of lead compound NSC746457 (Shen, J.; Woodward, R.; Kedenburg, J. P.; Liu, X. W.; Chen, M.; Fang, L. Y.; Sun; D. X.; Wang. P. G.J. Med. Chem. 2008, 51, 7417-7427) were performed, including the replacement of the trans-styryl moiety with a 2-substituted benzo-hetero aromatic ring and the introduction of a substituent onto the central methylene carbon. A promising chiral lead, S-(E)-3-(1-(1-(benzo[d]oxazol-2-yl)-2-methylpropyl)-1H-1,2,3- triazol-4-yl)-N-hydroxyacrylamide (12, NK-HDAC-1), was discovered and showed about 1 order of magnitude more potency than SAHA in both enzymatic and cellular assays. For the in vitro safety tests, NK-HDAC-1 was far less toxic to nontransformed cells than tumor cells and showed no significant inhibition activity against CYP-3A4. The pharmaceutical properties (LogD, solubility, liver micrsomal stability (t1/2), plasma stability (t1/2), and apparent permeability) strongly suggested that NK-HDAC-1 might be superior to SAHA in bioavailability and in vivo half-life.
- Hou, Jingli,Li, Zhonghua,Fang, Qinghong,Feng, Congran,Zhang, Hanwen,Guo, Weikang,Wang, Huihui,Gu, Guoxian,Tian, Yinping,Liu, Pi,Liu, Ruihua,Lin, Jianping,Shi, Yi-Kang,Yin, Zheng,Shen, Jie,Wang, Peng George
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supporting information; experimental part
p. 3066 - 3075
(2012/06/01)
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- Braces for the peptide backbone: Insights into structure-activity relationships of protease inhibitor mimics with locked amide conformations
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Flower power: Potent protease inhibitors containing triazolyl mimics of cis and trans backbone amides were engineered based on the structure of the sunflower trypsin inhibitor 1. The biologically relevant cis-Pro motif was successfully replaced with a non
- Tischler, Marco,Nasu, Daichi,Empting, Martin,Schmelz, Stefan,Heinz, Dirk W.,Rottmann, Philipp,Kolmar, Harald,Buntkowsky, Gerd,Tietze, Daniel,Avrutina, Olga
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supporting information; experimental part
p. 3708 - 3712
(2012/06/05)
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- Solid-phase synthesis of 2-aminoethyl glucosamine sulfoforms
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Mono- and disaccharides of sulfonated glucosamines (GlcN sulfoforms) conjugated to 2-aminoethyl linkers were generated by solid-phase synthesis. Orthogonally protected intermediates were tethered onto tritylated polystyrene resin beads, subjected to amodular sequence of deprotection and sulfonation steps, then cleaved from solid support without degradation of N- or O-sulfate esters using solvolytic conditions, and finally purified by reverse-phase HPLC to afford the title compounds. Copyright Taylor & Francis Group, LLC.
- Liu, Runhui,Wei, Alexander
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experimental part
p. 384 - 419
(2012/08/07)
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- α-Azido bisphosphonates: Synthesis and nucleotide analogues
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The first examples of α-azido bisphosphonates [(RO) 2P(O)]2CXN3 (1, R = i-Pr, X = Me; 2, R = i-Pr, X = H; 3, R = H, X = Me; 4, R = H, X = H) and corresponding β,γ- CXN3 dGTP (5-6) and α,β-CXN3 dATP (7-8) analogues are described. The individual diastereomers of 7 (7a/b) were obtained by HPLC separation of the dADP synthetic precursor (14a/b).
- Chamberlain, Brian T.,Upton, Thomas G.,Kashemirov, Boris A.,McKenna, Charles E.
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supporting information; experimental part
p. 5132 - 5136
(2011/08/09)
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- An efficient and general route to the synthesis of novel aminoglycosides for RNA binding
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An alternative and straightforward method to prepare aminoglycoside dimers and heterodimeric conjugates is reported. The novel type of modification may provide a promising way for the development of new ligands effectively targeting to RNA. Georg Thieme V
- Santana, Andrés G.,Bastida, ágatha,Del Campo, Teresa Martínez,Asensio, Juan Luis,Revuelta, Julia
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supporting information; experimental part
p. 219 - 222
(2011/03/20)
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- Fmoc-chemistry of a stable phosphohistidine analogue
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We report the synthesis of the phosphohistidine analogue, Fmoc-4-diethylphosphonotriazolylalanine 5 and its incorporation into peptides. Our synthesis of 5 has enabled us to demonstrate that the analogue is compatible with Fmoc-solid phase peptide synthesis (SPPS) conditions. Standard cleavage conditions yield the diethyl phosphonate-protected peptide, however this can be subsequently deprotected using trimethylsilyl bromide to yield the free phosphonic acid-containing peptides.
- McAllister, Tom E.,Nix, Michael G.,Webb, Michael E.
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supporting information; experimental part
p. 1297 - 1299
(2011/03/20)
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- A practical large-scale synthesis of cyclic RGD pentapeptides suitable for further functionalization through click' chemistry
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A multigram batch of the cyclo[Arg-Gly-Asp-d-Phe-Lys] and its N - azido derivative was accomplished via solution-phase synthesis using an epimerization-free fragment condensation. The C-terminus of d-Phe was protected as its tert-butyl ester. Fmoc (Arg, Gly, Asp, d-Phe) and Boc (Lys) groups were used to protect all N - termini. The Ts and NO2 groups, respectively were chosen to protect the guanidine group. The macrocyclization step (between d-Phe and l-Lys) was carried out under TBTU/HOBt or DPPA condensation conditions. Finally, the -amino group of the lysine residue was selectively converted into the azido group by a diazo-transfer reaction. Georg Thieme Verlag Stuttgart New York.
- Palecek, Jiri,Draeger, Gerald,Kirschning, Andreas
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experimental part
p. 653 - 661
(2011/04/15)
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- Solution-phase parallel synthesis and screening of anti-tumor activities from fenbufen and ethacrynic acid libraries
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The derivatives with fenbufen and ethacrynic acid core compounds was synthesized through a facial preparation of 1-amino-4-azidobutane. The subsequent coupling with 102 members of carboxylic acids afforded amide products. The in situ screening using colorimetric assay with 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide showed that fenbufen but not ethacrynic acid butyl amide members displayed the cytotoxicities to tumor cells substantially, including two human cell lines (MCF7 and A549) and two murine cell lines (C26 and TRAMP-C1). Three fenbufen analogs were found to have a good anti-tumor activity comparable to cisplatin.
- Su, Yuan-Hsiao,Chiang, Li-Wu,Jeng, Kee-Ching,Huang, Ho-Lien,Chen, Jenn-Tzong,Lin, Wuu-Jyh,Huang, Chia-Wen,Yu, Chung-Shan
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supporting information; experimental part
p. 1320 - 1324
(2011/04/16)
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- Universal peptidomimetics
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This paper concerns peptidomimetic scaffolds that can present side chains in conformations resembling those of amino acids in secondary structures without incurring excessive entropic or enthalpic penalties. Compounds of this type are referred to here as minimalist mimics. The core hypothesis of this paper is that small sets of such scaffolds can be designed to analogue local pairs of amino acids (including noncontiguous ones) in any secondary structure; i.e., they are universal peptidomimetics. To illustrate this concept, we designed a set of four peptidomimetic scaffolds. Libraries based on them were made bearing side chains corresponding to many of the protein-derived amino acids. Modeling experiments were performed to give an indication of kinetic and thermodynamic accessibilities of conformations that can mimic secondary structures. Together, peptidomimetics based on these four scaffolds can adopt conformations that resemble almost any combination of local amino acid side chains in any secondary structure. Universal peptidomimetics of this kind are likely to be most useful in the design of libraries for high-throughput screening against diverse targets. Consequently, data arising from submission of these molecules to the NIH Molecular Libraries Small Molecule Repository (MLSMR) are outlined.
- Ko, Eunhwa,Liu, Jing,Perez, Lisa M.,Lu, Genliang,Schaefer, Amber,Burgess, Kevin
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supporting information; experimental part
p. 462 - 477
(2011/04/16)
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- Enantioselective cyclopropenation of alkynes with acceptor/acceptor- substituted diazo reagents via Co(II)-based metalloradical catalysis
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The cobalt(II) complex of a new D2-symmetric chiral porphyrin 3,5-diMes-ChenPhyrin, [Co(P2)], has been shown to be a highly effective chiral metalloradical catalyst for enantioselective cyclopropenation of alkynes with acceptor/acceptor-substituted diazo reagents, such as α- cyanodiazoacetamides and α-cyanodiazoacetates. The [Co(P2)]-mediated metalloradical cyclopropenation is suitable to a wide range of terminal aromatic and related conjugated alkynes with varied steric and electronic properties, providing the corresponding trisubstituted cyclopropenes in high yields with excellent enantiocontrol of the all-carbon quaternary stereogenic centers. In addition to mild reaction conditions, the Co(II)-based metalloradical catalysis for cyclopropenation features a high degree of functional group tolerance.
- Cui, Xin,Xu, Xue,Lu, Hongjian,Zhu, Shifa,Wojtas, Lukasz,Zhang, X. Peter
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supporting information; experimental part
p. 3304 - 3307
(2011/04/24)
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- Versatile site-specific conjugation of small molecules to siRNA using click chemistry
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We have previously demonstrated that conjugation of small molecule ligands to small interfering RNAs (siRNAs) and anti-microRNAs results in functional siRNAs and antagomirs in vivo. Here we report on the development of an efficient chemical strategy to make oligoribonucleotide-ligand conjugates using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) or click reaction. Three click reaction approaches were evaluated for their feasibility and suitability for high-throughput synthesis: the CuAAC reaction at the monomer level prior to oligonucleotide synthesis, the solution-phase postsynthetic "click conjugation", and the "click conjugation" on an immobilized and completely protected alkyne-oligonucleotide scaffold. Nucleosides bearing 5′-alkyne moieties were used for conjugation to the 5′-end of the oligonucleotide. Previously described 2′-and 3′-O-propargylated nucleosides were prepared to introduce the alkyne moiety to the 3′ and 5′ termini and to the internal positions of the scaffold. Azido-functionalized ligands bearing lipophilic long chain alkyls, cholesterol, oligoamine, and carbohydrate were utilized to study the effect of physicochemical characteristics of the incoming azide on click conjugation to the alkyne-oligonucleotide scaffold in solution and on immobilized solid support. We found that microwave-assisted click conjugation of azido-functionalized ligands to a fully protected solid-support bound alkyne-oligonucleotide prior to deprotection was the most efficient "click conjugation" strategy for site-specific, high-throughput oligonucleotide conjugate synthesis tested. The siRNA conjugates synthesized using this approach effectively silenced expression of a luciferase gene in a stably transformed HeLa cell line.(Figure Presented)
- Yamada, Takeshi,Peng, Chang Geng,Matsuda, Shigeo,Addepalli, Haripriya,Jayaprakash, K. Narayanannair,Alam, Md. Rowshon,Mills, Kathy,Maier, Martin A.,Charisse, Klaus,Sekine, Mitsuo,Manoharan, Muthiah,Rajeev, Kallanthottathil G.
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supporting information; experimental part
p. 1198 - 1211
(2011/04/26)
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- Triazole ligands reveal distinct molecular features that induce histaine H4 receptor affinity and subtly govern H4/H3 subtype selectivity
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The histamine H3 (H3R) and H4 (H 4R) receptors attract considerable interest from the medicinal chemistry community. Given their relatively high homology yet widely differing therapeutic promises, ligand selectivity for the two receptors is crucial. We interrogated H4R/H3R selectivities using ligands with a [1,2,3]triazole core. Cu(I)-assisted "click chemistry" was used to assemble diverse [1,2,3]triazole compounds (6a-w and 7a-f), many containing a peripheral imidazole group. The imidazole ring posed some problems in the click chemistry putatively due to Cu(II) coordination, but Boc protection of the imidazole and removal of oxygen from the reaction mixture provided effective strategies. Pharmacological studies revealed two monosubstituted imidazoles (6h,p) with 4R affinities and >10-fold H 4R/H3R selectivity. Both compounds possess a cycloalkylmethyl group and appear to target a lipophilic pocket in H 4R with high steric precision. The use of the [1,2,3]triazole scaffold is further demonstrated by the notion that simple changes in spacer length or peripheral groups can reverse the selectivity toward H3R. Computational evidence is provided to account for two key selectivity switches and to pinpoint a lipophilic pocket as an important handle for H4R over H3R selectivity.
- Wijtmans, Maikel,De Graaf, Chris,De Kloe, Gerdien,Istyastono, Enade P.,Smit, Judith,Lim, Herman,Boonnak, Ratchanok,Nijmeijer, Saskia,Smits, Rogier A.,Jongejan, Aldo,Zuiderveld, Obbe,De Esch, Iwan J. P.,Leurs, Rob
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supporting information; experimental part
p. 1693 - 1703
(2011/05/05)
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- A convenient entry to new C-7-modified colchicinoids through azide alkyne [3+2] cycloaddition: Application of ring-contractive rearrangements
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Reliable procedures for the preparation of azides derived from colchicine (1), allocolchicine (3) and N-acetylcolchinol (4a) were developed. These azides were then employed in Cu-catalyzed Huisgen-Sharpless [3+2] cycloaddition ("click") reactions with alkynes under microwave irradiation. The method developed opens a convenient and efficient access to libraries of new C-7-modified colchicinoids (triazole derivatives). In addition, a plausible mechanistic rationale for the colchicine-allocolchicine rearrangement is suggested. The Japan Institute of Heterocyclic Chemistry.
- Nicolaus, Norman,Reball, Jens,Sitnikov, Nikolay,Velder, Janna,Termath, Andreas,Fedorov, Alexey Yu.,Schmalz, Hans-Guenther
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experimental part
p. 1585 - 1600
(2011/06/17)
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- Introduction of aromatic group on 4′-OH of α-GalCer manipulated NKT cell cytokine production
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The glycosphingolipid α-GalCer has been found to influence mammalian immune system significantly through the natural killer T cells. Unfortunately, the pre-clinical and clinical studies revealed several critical disadvantages that prevented the therapeutic application of α-GalCer in treating cancer and other diseases. Recently, the detailed illustration of the CD1d/α-GalCer/NKT TCR complex crystal structural, together with other latest structural and biological understanding on glycolipid ligands and NKT cells, provided a new platform for developing novel glycolipid ligands with optimized therapeutic effects. Here, we designed a series of novel aromatic group substituted α-GalCer analogues. The biological activity of these analogues was characterized and the results showed the unique substitution group manipulated the immune responses of NKT cells. Computer modeling and simulation study indicated the analogues had unique binding mode when forming CD1d/glycolipid/NKT TCR complex, comparing to original α-GalCer.
- Zhang, Wenpeng,Xia, Chengfeng,Nadas, Janos,Chen, Wenlan,Gu, Li,Wang, Peng George
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experimental part
p. 2767 - 2776
(2011/06/19)
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- Maintaining biological activity by using triazoles as disufide bond mimetics
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Click into place: Tachyplesin-I (TP-I) analogues in which both disulfide bridges (1) have been replaced with triazoles (2) represent structural mimetics of TP-I that display similar or slightly improved antibacterial activity. Optimized structures were obtained by replacing the cysteine residues in TP-I by azido- and alkyno-functionalized amino acids. Copyright
- Holland-Nell, Kai,Meldal, Morten
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supporting information; experimental part
p. 5204 - 5206
(2011/06/26)
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- Synthesis and biological evaluation of modified 2-deoxystreptamine dimers
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Aminoglycosides are powerful antibiotics, but the emergence of resistant bacterial strains has prompted the search for analogues with better pharmacological profiles. The synthesis of 2-deoxystreptamine (2-DOS) dimers linked by polyamines and analogues based on furylcarbopeptoid skeletons is described. Potent and selective ligands for bacterial 16S rRNA were identified using microarray techniques by determining the affinity of these derivatives toward bacterial and human ribosomal RNAs. Georg Thieme Verlag Stuttgart - New York.
- Coste, Gerald,Horlacher, Tim,Molina, Lidia,Moreno-Vargas, Antonio J.,Carmona, Ana T.,Robina, Inmaculada,Seeberger, Peter H.,Gerber-Lemaire, Sandrine
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experimental part
p. 1759 - 1770
(2011/07/30)
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- A practical system to synthesize the multiple-substituted 2,5-dihydrofuran by the intermolecular dipolar cycloaddition reactions involving acceptor/acceptor-substituted diazo reagents
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A practical system for synthesizing the multiple-substituted 2,5-dihydrofuran through intermolecular dipolar cycloaddition reactions of acceptor/acceptor diazo reagents, aldehydes, and acetylenedicarboxylate was developed. The reactions proceeded effectively under ambient temperature with low reactant ratios. The control reactions revealed that there are two competitive paths: one forms 1,3-dioxolane and the other forms 2,5-dihydrofuran. These two paths could be controlled by modifying the steric hindrance of the diazo reagents.
- Zhu, Shifa,Chen, Lijuan,Wang, Chao,Liang, Renxiao,Wang, Xiujun,Ren, Yanwei,Jiang, Huanfeng
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experimental part
p. 5507 - 5515
(2011/08/06)
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- Resolution, absolute configuration, and synthetic transformations of 7-amino-tetrahydroindazolones
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The chiral resolution of 7-amino-1-aryl-4,5,6,7-tetrahydro-indazol-4-ones was achieved via salt formation with O,O′-dibenzoyl tartaric acid. The transformation of enantiomerically enriched 7-amino-THIs into their corresponding azides proceeds with no decr
- Strakova, Inta,Kumpia, Ilze,Rjabovs, Vitlijs,Lugiina, Jevgeija,Belyakov, Sergey,Turks, Maris
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experimental part
p. 728 - 739
(2011/08/06)
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- The 3-deoxy analogue of α-GalCer: Disclosing the role of the 4-hydroxyl group for CD1d-mediated NKT Cell activation
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KRN7000, or α-GalCer, is a potent agonist for natural killer T (NKT) cells. The 3-hydroxyl group of its phytosphingosine moiety is important for activating NKT cells, whereas its 4-hydroxyl group is perceived to be less crucial. To experimentally determine the role of the 4-hydroxyl group, we synthesized the 3-deoxy analogue of α-GalCer. It was found that 3-deoxy-α-GalCer induced potent cytokine responses from NKT cells, comparable to those of both α-GalCer and 4-deoxy-α-GalCer. This result and our docking studies suggest that the effects of an absence of the 3-hydroxyl group are compensated by the presence of a hydroxyl group at the C-4 position. Thus, we conclude that the 4-hydroxyl group of α-GalCer is as important to the mechanism of action as the 3-hydroxyl group and that the two hydroxyl groups could play individual and cooperative roles in orienting the glycolipid into the proper position in CD1d to be recognized by the T cell receptor of NKT cells.
- Baek, Dong Jae,Seo, Jeong-Hwan,Lim, Chaemin,Kim, Jae Hyun,Chung, Doo Hyun,Cho, Won-Jea,Kang, Chang-Yuil,Kim, Sanghee
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supporting information; experimental part
p. 544 - 548
(2011/09/16)
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- Conjugate of neamine and 2-deoxystreptamine mimic connected by an amide bond
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An amino-functionalized 2-deoxystreptamine (2-DOS) mimic was conjugated by an amide bond to a neamine moiety containing a carboxylic acid in ring II. A library of A-site RNA and its mutants was prepared to examine RNA binding characteristics of the additi
- Udumula, Venkatareddy,Chittapragada, Maruthi,Marble, Jorden B.,Dayton, Daniel L.,Ham, Young Wan
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supporting information; body text
p. 4713 - 4715
(2011/09/20)
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- Solid-phase total synthesis of (-)-apratoxin a and its analogues and their biological evaluation
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Two approaches for the solid-phase total synthesis of apratoxinA and its derivatives were accomplished. In synthetic route A, the peptide was prepared by the sequential coupling of the corresponding amino acids on trityl chloride SynPhase Lanterns. After cleavage from the polymer-support, macrolactamization of 10, followed by thiazoline formation, provided apratoxinA. This approach, however, resulted in low yield because the chemoselectivity was not sufficient for the formation of the thiazoline ring though its analogue 33 was obtained. However, in synthetic route B, a cyclization precursor was prepared by solid-phase peptide synthesis by using amino acids 13-15 and 18. The final macrolactamization was performed in solution to provide apratoxin A in high overall yield. This method was then successfully applied to the synthesis of apratoxin analogues. The cytotoxic activity of the synthetic derivatives was then evaluated. The epimer 34 was as potent as apratoxinA, and O-methyl tyrosine can be replaced by 7-azidoheptyl tyrosine without loss of activity. The 1,3-dipolar cycloaddition of 38 with phenylacetylene was performed in the presence of a copper catalyst without affecting the thiazoline ring. Solid Approach: Two routes for the solid-phase total synthesis of apratoxinA have been described. On the basis of this method, its analogues were synthesized and their biological activity has been evaluated. Copyright
- Doi, Takayuki,Numajiri, Yoshitaka,Takahashi, Takashi,Takagi, Motoki,Shin-Ya, Kazuo
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supporting information; experimental part
p. 180 - 188
(2011/10/08)
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- Lipid and sulfur substituted prenylcysteine analogs as human Icmt inhibitors
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Inhibition of isoprenylcysteine carboxyl methyltransferase (Icmt) offers a promising strategy for K-Ras driven cancers. We describe the synthesis and inhibitory activity of substrate-based analogs derived from several novel scaffolds. Modifications of bot
- Bergman, Joel A.,Hahne, Kalub,Hrycyna, Christine A.,Gibbs, Richard A.
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supporting information; experimental part
p. 5616 - 5619
(2011/10/13)
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- Concise, stereocontrolled synthesis of the citrinadin B core architecture
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A concise, stereocontrolled synthesis of the citrinadin B core architecture from scalemic, readily available starting materials is disclosed. Highlights include ready access to both cyclic tryptophan tautomer and trans-2,6- disubstituted piperidine fragme
- Guerrero, Carlos A.,Sorensen, Erik J.
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supporting information; experimental part
p. 5164 - 5167
(2011/12/02)
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- Amphiphilic 1-deoxynojirimycin derivatives through click strategies for chemical chaperoning in N370S gaucher cells
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In Gaucher disease (GD), mutant β-glucocerebrosidases (β-GCase) that are misfolded are recognized by the quality control machinery of the endoplasmic reticulum (ER) and degraded proteolytically. Hydrophobic iminosugars can be used as pharmacological chaperones to provide an improvement in the folding of the enzyme and promote trafficking from the ER. We have developed here an efficient click procedure to tether hydrophobic substituents to N-azidopropyl-1-deoxynojirimycin. A set of 14 original iminosugars was designed and evaluated for inhibition of commercially available glucosidases. Most of the compounds were micromolar inhibitors of those enzymes. In vitro inhibition assays with the N370S β-GCase revealed that the sublibrary containing the derivatives with aromatic aglycons displayed the highest inhibitory potency. Chaperone activity of the whole set of synthetic compounds was also explored in mutant Gaucher cells. The most active compound gave a nearly 2-fold increase in enzyme activity at 20 μM, a significantly higher value than the 1.33-fold recorded for the reference compound N-nonyl-1-deoxynojirimycin (N-nonyl-DNJ). As previously reported with bicyclic sp2-iminosugars (Luan, Z.; Higaki, K.; Aguilar-Moncayo, M.; Ninomiya, H.; Ohno, K.; Garcia-Moreno, M. I.; Ortiz Mellet, C.; Garcia Fernandez, J. M.; Suzuki, Y. ChemBioChem 2009, 10, 2780), in vitro inhibition of β-GCase measured for the compounds did not correlate with the cellular chaperone activity. The potency of new iminosugar chaperones is therefore not predictable from structureactivity relationships studies based on the in vitro β-GCase inhibition. (Figure presented)
- Diot, Jennifer D.,Moreno, Isabel Garcia,Twigg, Gabriele,Mellet, Carmen Ortiz,Haupt, Karsten,Butters, Terry D.,Kovensky, Jose,Gouin, Sebastien G.
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experimental part
p. 7757 - 7768
(2011/12/03)
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- Design, synthesis and biological evaluation of mannosyl triazoles as FimH antagonists
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Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is one of the most prevalent infectious diseases. Particularly affected are women, who have a 40-50% risk to experience at least one symptomatic UTI episode at some time during
- Schwardt, Oliver,Rabbani, Said,Hartmann, Margrit,Abgottspon, Daniela,Wittwer, Matthias,Kleeb, Simon,Zalewski, Adam,Smie?ko, Martin,Cutting, Brian,Ernst, Beat
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experimental part
p. 6454 - 6473
(2011/12/14)
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- Water-soluble prodrug of antimicrotubule agent plinabulin: Effective strategy with click chemistry
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Click for improved solubility: A water-soluble prodrug of plinabulin was designed and synthesized efficiently by using click chemistry in three steps (see scheme). The product was highly water-soluble, and the parent compound could be regenerated by ester
- Yakushiji, Fumika,Tanaka, Hironari,Muguruma, Kyohei,Iwahashi, Takahiro,Yamazaki, Yuri,Hayashi, Yoshio
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supporting information; experimental part
p. 12587 - 12590
(2011/12/21)
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- CONSTRUCTION AND SCREENING OF SOLUTION-PHASE DERIVED LIBRARY OF FENBUFEN AND ETHACRYNIC ACID
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A process for synthesizing and screening solution phase derived libraries of fenbufen and ethacrynic acid is provided in the present invention. Compounds in the present invention having cytotoxicities are useful for a variety of therapeutic applications.
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Page/Page column 23
(2012/01/03)
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- Multivalent glycocluster design through directed evolution
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Selection with modified aptamers: A method is described for design of glycocluster ligands by directed evolution. Glycan azides are attached to a library of alkyne-containing DNA sequences. DNA sequences which cluster the glycans best for multivalent bind
- MacPherson, Iain S.,Temme, J. Sebastian,Habeshian, Sevan,Felczak, Krzysztof,Pankiewicz, Krzysztof,Hedstrom, Lizbeth,Krauss, Isaac J.
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supporting information; experimental part
p. 11238 - 11242
(2012/02/03)
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- Towards the identification of unknown neuropeptide precursor-processing enzymes: Design and synthesis of a new family of dipeptidyl phosphonate activity probes for substrate-based protease identification
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Specific proteolytic processing of inactive precursors is an exquisite cellular mechanism that triggers the activation of numerous physiologic peptides and proteins. This process ensures the generation of biologically active peptides, such as many neurope
- Sabidó, Eduard,Tarragó, Teresa,Giralt, Ernest
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supporting information; experimental part
p. 8350 - 8355
(2011/02/22)
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- Total synthesis of celogentin C by stereoselective C-H activation
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(Figure Presented) A total gent: Inspired by the biosynthesis of celogentin C, a highly stereoselective and efficient palladium-catalyzed C-H functionalization strategy is employed to construct the key Leu-Trp linkage of this bicyclic compound. A streamlined synthesis is completed in 23 steps from simple amino acid building blocks.
- Feng, Yiqing,Chen, Gong
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supporting information; experimental part
p. 958 - 961
(2010/06/11)
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- "click" synthesis of nonsymmetrical bis(1,2,3-triazoles)
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Chemical Fig. Repretation Unsymmetrically 1,1'-disubstituted 4,4'-bis-1 H-1,2,3-triazoles 4 have been prepared from 4-ethynyl-1,2,3-triazoles 5 and azides. Following a "double-click" strategy, two complementary approaches were implemented for the preparation of the key 4-ethynyltriazole Intermediates 5: (a) the stepwise Swern oxidatlon/Ohira-Bestman alkynylation of readily available 4-hydroxymethyl-1,2,3-triazoles 8 and (b) the stepwise cycloaddition of TMS-1,4-butadiyne 9. The method is highlighted by Its compatibility with orthogonally protected and functlonallzed saccharide-peptide hybrids and its ability to be extended to the trlsubstituted counterparts 12.
- Aizpurua, Jesus M.,Azcune, Itxaso,Fratila, Raluca M.,Balentova, Eva,Sagartzazu-Aizpurua, Malaien,Miranda, Jose I.
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supporting information; experimental part
p. 1584 - 1587
(2010/06/16)
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- PREPARATION OF DIAZO AND DIAZONIUM COMPOUNDS
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A method for making diazo-compounds, diazonium salts thereof and other protected forms of these compounds. Diaz-compounds are prepared by reaction of a tertiary phosphine reagent carrying a reactive carbonyl group with an azide. The reaction can also generate an acyl triazene which can be converted thermally or by addition of base to form the diazo-compound or the acyl triazene can be isolated. The method is particularly useful for conversion of azides carrying one or more electron withdrawing groups to diazo-compounds. The method can be carried out in aqueous medium under mild conditions and is particularly useful for conversion of azido sugars to diazo-compound and diazonium salts thereof under physiological conditions. Tertiary phosphine reagents, particularly those that are water-soluble, and precursors for preparation of the reagents are provided.
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Page/Page column 27-28
(2010/06/13)
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- Bioorthogonal chemical reporters for monitoring protein acetylation
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"Chemical equation presented" Protein acetylation is a key post-translational modification that regulates diverse biological activities in eukaryotes. Here we report bioorthogonal chemical reporters that enable direct in-gel fluorescent visualization and
- Yang, Yu-Ying,Ascano, Janice M.,Hang, Howard C.
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supporting information; experimental part
p. 3640 - 3641
(2010/05/15)
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- Synthesis of neamine-carboline conjugates for RNA binding and their antibacterial activities
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Three types of neamine-β-carboline conjugates were synthesized in good yields by the coupling of neamine and β-carboline-3-carboxylic acids using aliphatic diamine as a linker. The binding properties of these conjugates to 16S rRNA and 18S rRNA were evaluated by surface plasmon resonance (SPR), showing that some conjugates had stronger binding affinities than neamine. In vitro antimicrobial activities were also evaluated and the results showed that some synthetic compounds exhibited better antibacterial activities than neamine. The preliminary structure-activity relationship was discussed. The present experimental data demonstrated that synthetic neamine-carboline conjugates might hold the potential as new antibiotics.
- Wu, Shan,Fu, Yunsha,Yan, Ribai,Wu, Yanfen,Lei, Xiaoping,Ye, Xin-Shan
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experimental part
p. 3433 - 3440
(2010/06/19)
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