SYNTHETIC MACROMOLECULAR INHIBITORS OF HUMAN-LEUKOCYTE ELASTASE .1. SYNTHESIS OF PEPTIDYL CARBAMATES BOUND TO WATER-SOLUBLE POLYMERS - LY-ALPHA,BETA-[N-(2-HYDROXYETHYL)-D,L-ASPARTAMIDE] AND POLY-ALPHA-[N-5-(2-HYDROXYETHYL)-L-GLUTAMINE]

The design and synthesis of macromolecular peptidyl carbamate inhibito rs of human leukocyte elastase (HLE), based on coupling of a low-molec ular-weight peptidyl carbamate, succinylalanylalanylprolylmethyl isopr opyl carbamate, with a linear hydrophilic polymer, ly-alpha,beta-[N-(2 -hydroxyethyl)-D,L-aspartamide] or poly-alpha-[N-5-(2-hydroxyethyl)-L- glutamine], is described. The covalent linkage between a flexible line ar polymer and a peptidyl carbamate inhibitor of HLE did not compromis e in vitro inhibitory capacity. The macromolecular peptidyl carbamates reported here represent a novel class of elastase inhibitors with a K -i ranging from 35.5 to 2.0 nM.