Novel 3-amino-2-hydroxy acids containing protease inhibitors. Part 1: Synthesis and kinetic characterization as aminopeptidase P inhibitors

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• 作者：Angela Stö ; ckel-Maschek ; Beate Stiebitz ; Regine Koelsch and Klaus Neubert
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2005
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：2005
• 卷：13
• 期：16
• 页码：4806-4820
• 文件大小：512 K

摘要

Novel, potent inhibitors of aminopeptidase P, containing a 3-amino-2-hydroxy acid and a proline or a proline analogues, have been prepared. One part of the bestatin-derived inhibitors was found to inhibit APP from Escherichia coli and from rat intestine according to a mixed-type mechanism, with K_i values up to 1.26 μM. The other compounds, 3-amino-2-hydroxy acyl prolines of a different configuration, inhibit APP competitively, according to a slow-binding mechanism, with K_i values in the nanomolar up to the micromolar range.