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

Basic Information

ID: ALA1131500

Journal: J Med Chem

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

Authors: Devadas B, Freeman SK, McWherter CA, Kishore NS, Lodge JK, Jackson-Machelski E, Gordon JI, Sikorski JA.

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 (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.

CiteXplore: 9526574

DOI: 10.1021/jm980001q

Patent ID: