A chiral recognition element with an unusual size constraint affects the potency and selectivity for peptidomimetic inhibitors of Candida albicans myristoyl-CoA:protein N-myristoyltransferase

被引：11

作者：

Devadas, B ^{[1
]}

Freeman, SK ^{[1
]}

McWherter, CA ^{[1
]}

Kuneman, DW ^{[1
]}

Vinjamoori, DV ^{[1
]}

Sikorski, JA ^{[1
]}

机构：

[1] MONSANTO CO,MONSANTO CORP RES,DEPT ANALYT CHEM,ST LOUIS,MO 63167

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1996年 / 6卷 / 16期

关键词：

D O I：

10.1016/0960-894X(96)00354-X

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Beginning with a high affinity octapeptide substrate GLYASKLS-NH2 (2, K-m = 0.6 mu M) a potent dipeptide Candida NMT inhibitor 18a (IC50 = 20 nM) was identified. The structure-activity relationship studies suggest that the alpha-methyl group with an (R) configuration at the benzylic position, imparts maximum selectivity and potency against Candida NMT. The synthetic design, chiral separation of the diastereomers 18a and 18b, and in vitro potency of this novel class of NMT inhibitors are described. Copyright (C) 1996 Elsevier Science Ltd.

引用

页码：1977 / 1982

页数：6

共 11 条

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