Peptide inhibitors of CDK2-cyclin A that target the cyclin recruitment-site: Structural variants of the C-terminal Phe

被引：16

作者：

Atkinson, GE

Cowan, A

McInnes, C

Zheleva, DI

Fischer, PM

Chan, WC

机构：

[1] Univ Nottingham, Sch Pharmaceut Sci, Nottingham NG7 2RD, England

[2] Cyclacel Ltd, Dundee DD1 5JJ, Scotland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 18期

关键词：

D O I：

10.1016/S0960-894X(02)00508-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A focused series of octapeptides based on the lead compound H-His-Ala-Lys-Arg-Arg-Leu-Ile-Phe-NH2 1, in which the C-terminal phenylalanine residue was replaced by alpha and/or beta-modified variants, was synthesized using solid-phase chemistry. Both the L-threo-beta-hydroxy-phenylalanine (beta-phenylserine, Pse) and (2S)-phenylalaninol derivatives, as competitive binders at the cyclin-recruitment site, displayed potent inhibitory activity towards the CDK2-cyclin A complex. Unexpectedly, the D-threo-Pse derivatives also showed inhibitory activity. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：2501 / 2505

页数：5

共 20 条

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