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

Beginning with a high affinity octapeptide substrate GLYASKLS-NH2 (2, K-m = 0.6 mu M) a potent dipeptide Candida NMT inhibitor 18a (IC50 = 2 0 nM) was identified. The structure-activity relationship studies sugg est that the alpha-methyl group with an (R) configuration at the benzy lic 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 ar e described. Copyright (C) 1996 Elsevier Science Ltd.