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Jean-Alain Fehrentz Corine Genu-Dellac Muriel Amblard Franclois Winternitz Albert Loffet Jean Martinez 《Journal of peptide science》1995,1(2):124-131
N-Urethane-protected N-carboxyanhydrides (UNCAs) are very reactives. They have been successfully used in peptide synthesis, in both solution and solid phase. We have demonstrated that UNCAs are interesting starting materials for the synthesis of various amino acid derivatives. Chemoselective reduction of UNCAs with sodium borohydride led the corresponding N-protected β amino alcohols. Reaction of UNCAs with Meldrum's acid, followed by cyclisation, yielded enantiomerially pure tetramic acid derivatives. Diastereoselective reduction of tetramic acid derivatives produced (4S,5S)-N-alkoxycarbonyl-4-hydroxy-5-alkylpyrrolidin-2-ones derived from amino acids, which after hydrolysis yielded statine and statine analogues. Tetramic acid derivatives could also be obtained by reaction of UNCAs with benzyl ethyl followed by hydrogenolytic deprotection and decarboxylation. UNCAs also reacted with phosphoranes to produce the ketophosphorane in excellent yields. Subsequent oxidation with oxone or with [bis(acetoxy)-iodol]-benzene produced vicinal tricarbonyl derivatives. These reactions usually proceeded smoothly and with high yields. 相似文献
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Structure-based subsite specificity mapping of human cathepsin D using statine-based inhibitors. 下载免费PDF全文
P. Majer J. R. Collins S. V. Gulnik J. W. Erickson 《Protein science : a publication of the Protein Society》1997,6(7):1458-1466
Human cathepsin D is a lysosomal aspartic protease that has been implicated in breast cancer metastasis and Alzheimer's disease. Based on a crystal structure of a human cathepsin D-pepstatin A complex, a series of statine-containing inhibitors was designed, synthesized, and tested for inhibitory activity toward the enzyme in vitro. The compounds were modified systematically at individual positions (P4, P3, P2, P1, and P2t) with the aim of mapping the cathepsin D subsite preferences. The experimentally obtained SAR data were correlated on the basis of molecular modeling. Side-chain preferences for the peptidomimetic inhibitors differed from those found previously using peptide substrates (Scarborough PE et al., 1993, Protein Sci 2:264-276). In addition, the effects of single side-chain modifications were often nonadditive. Structure-activity relationships, modeling, and thermodynamic analysis indicated that entropy plays a major stabilizing role in inhibitor binding to cathepsin D. 相似文献
3.
Cosimo D. Cadicamo Vivian Asante Morhaf Abu Ammar Claudia Borelli Hans C. Korting Beate Koksch 《Journal of peptide science》2009,15(4):272-277
The synthetic route to pepstatin derivatives by a solid phase peptide synthesis using either O‐protected or O‐unprotected statine as a building block has been investigated. Statine was prepared according to a modified literature procedure, whereas protection of its 3‐hydroxyl moiety using tert‐butyldimethylsilylchloride (TBSCl) provided the novel O‐TBS‐protected statine building block. The O‐tert‐butyldimethylsilyl (TBS)‐protected statine approach provides an improved synthetic strategy for the preparation of statine‐containing peptides as demonstrated by the synthesis of the pepstatin analogue iva‐Val‐Leu‐Sta‐Ala‐Sta. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
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Pascal Verdié Gilles Subra Pierre Chevallet Muriel Amblard Jean Martinez 《International journal of peptide research and therapeutics》2007,13(1-2):337-343
As part of our efforts to design constrained peptide mimics and introduce them in peptide sequences, we set up the synthesis
of racemic N-Fmoc protected hydroxypyrrolidine by reduction of the corresponding oxopyrroline. Hydroxypyrrolidines are synthesized
using amino acid building block and β-ketoester via a 4-steps solid supported route on Wang resin beads. The hydroxypyrrolidine template can be seen as a constrained mimic of
statine. As proof of concept, the pseudopeptide JMV 2776, incorporating this new statine mimic has been synthesized. We replaced
the phenyl statine building block in the sequence of known BACE 1/2 inhibitors by 5-benzyl 2-methyl 4-hydroxypyrrolidine,
using conventional Fmoc SPPS on Rink amide PS resin.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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