Novel biologically active nonpeptidic inhibitors of myristoylCoArprotein NMyristoyltransferase

Balekudru Devadas, Sandra K. Freeman, Charles A. McWherter, Nandini S. Kishore, Jennifer Lodge, Emily Jackson-Machelski, Jeffrey Gordon, James A. Sikorski

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

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 CR)-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.

Original languageEnglish
Pages (from-to)996-1000
Number of pages5
JournalJournal of Medicinal Chemistry
Volume41
Issue number6
DOIs
StatePublished - Mar 12 1998

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