Synthetic macromolecular inhibitors of human leukocyte elastase. 1. Synthesis of peptidyl carbamates bound to water-soluble polymers: poly-alpha,beta-[N-(2-hydroxyethyl)-D,L-aspartamide] and poly-alpha-[N5-(2-hydroxyethyl)-L-glutamine].
The design and synthesis of macromolecular peptidyl carbamate inhibitors of human leukocyte elastase (HLE), based on coupling of a low-molecular-weight peptidyl carbamate, succinylalanylalanylprolylmethyl isopropyl carbamate, with a linear hydrophilic polymer, poly-alpha,beta-[N-(2-hydroxyethyl)-D,L-aspartamide] or poly-alpha-[N5-(2-hydroxyethyl)-L-glutamine], is described. The covalent linkage between a flexible linear polymer and a peptidyl carbamate inhibitor of HLE did not compromise in vitro inhibitory capacity. The macromolecular peptidyl carbamates reported here represent a novel class of elastase inhibitors with a Ki ranging from 35.5 to 2.0 nM.
Rypacek
F
F
Institute of Macromolecular Chemistry, Czechoslovak Academy of Sciences, Prague.
Banks
W R
WR
Noskova
D
D
Digenis
G A
GA
D000595:Amino Acid Sequence; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D019272:Leukocyte Elastase; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D010455:Peptides / Q000737:chemistry*; D012995:Solubility; D014867:Water
D002219:Carbamates; D010455:Peptides; C008965:alpha,beta-poly((2-hydroxyethyl)-aspartamide); D014867:Water; C027887:poly-N(5)-(2-hydroxyethyl)glutamine; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase