The effect of a peptide aldehyde reversible inhibitor of elastase on a human leucocyte elastase-induced model of emphysema in the hamster.
The peptide aldehyde Ro 31-3537, N alpha-(1-adamantanesulphonyl)-N epsilon-(4-carboxybenzoyl)-L-lysyl-L-alanyl-L- valinal, is a reversible competitive, hydrophilic, specific inhibitor of elastase. Its Ki against human leucocyte elastase is 6 x 10(-8) M. The effect of this compound has been studied on a model of emphysema in the hamster induced by multiple sequential intratracheal doses of human leucocyte elastase. Concomitant intratracheal dosing of 200 micrograms of inhibitor with the enzyme significantly reduces lung damage as measured by quasi-static lung compliance and by histological assessment of the emphysema.
Department of Biology, Roche Products Ltd, Welwyn Garden City, U.K.
A J
AJ
Kennedy
A
A
Cline
U M
UM
Ney
W H
WH
Johnson
N A
NA
Roberts
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D006224:Cricetinae; D004195:Disease Models, Animal; D019272:Leukocyte Elastase; D008168:Lung / Q000473:pathology; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D008647:Mesocricetus; D009842:Oligopeptides / Q000494:pharmacology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D012129:Respiratory Function Tests
D009842:Oligopeptides; C045401:N(alpha)-(1-adamantanesulfonyl)-N(epsilon)-(4-carboxybenzoyl)lysyl-alanyl-valinal; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D000218:Adamantane