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 sequenc es with lysine at the P-3 and ornithine at the Pq positions were synthesize d. Most of the inhibitors with large molecular weights showed high inhibito ry capacity with Ki values as low as 10(-8) M. Compounds immobilized on pol y,alpha,beta-[N- (2-hydroxyethyl)-D,L-aspartamide](PHEA) polymers with an a verage molecular weight of 36,000 showed higher inhibitory capacity than th eir free forms.