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 P3 and ornithine at the P4 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.
Li-Pan
Z S
ZS
Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
Joshi
H V
HV
Digenis
G A
GA
D015195:Drug Design; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D008970:Molecular Weight; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D007202:Indicators and Reagents; D010455:Peptides; D015842:Serine Proteinase Inhibitors; D013859:Thiocarbamates; D019272:Leukocyte Elastase