Synthesis and Mechanism of Action of Novel Thiocarbamate Inhibitors of Human Leukocyte Elastase.
Several peptidyl thiocarbamate inhibitors of human leukocyte elastase were synthesized in the molecular weight range of 700-800. Two different sequences with lysine at the P(3) and ornithine at the P(4) positions were synthesized. Most of the inhibitors with large molecular weights showed high inhibitory capacity with Ki values as low as 10(-8) M. Compounds immobilized on poly,alpha,beta-[N-(2-hydroxyethyl)-d,l-aspartamide] (PHEA) polymers with an average molecular weight of 36,000 showed higher inhibitory capacity than their free forms.
Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
Sky Li-Pan Z
HV
Joshi
GA
Digenis