Novel biologically active nonpeptidic inhibitors of myristoylCoA:protein N-myristoyltransferase

被引：43

作者：

Devadas, B ^{[1
]}

Freeman, SK

McWherter, CA

Kishore, NS

Lodge, JK

Jackson-Machelski, E

Gordon, JI

Sikorski, JA

机构：

[1] Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA

[2] GD Searle & Co, Dept Med & Struct Chem, St Louis, MO 63198 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1998年 / 41卷 / 06期

关键词：

D O I：

10.1021/jm980001q

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new class of biologically active nonpeptidic inhibitors of Candida albicans NMT has been synthesized starting from the octapeptide ALYASKLS-NH2 (2). The synthetic strategy entailed the preparation of novel protected Ser-Lys mimics 9 and 12 from (S)- or (R)-3-iodotyrosine and then grafting key enzyme recognition elements in a stepwise manner. Like 2, compounds 16, 17, and 18 are competitive Candida NMT inhibitors that bind to the peptide recognition site of the enzyme. Moreover, 16-18 have an affinity comparable to that of 2 even though they are devoid of peptide bonds. In contrast to 2, these nonpeptidic inhibitors exhibit antifungal activity.

引用

页码：996 / 1000

页数：5

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