Inhibitors of human leucocyte elastase. Peptides incorporating an α-azanorvaline residue or a thiomethylene linkage in place of a peptide bond

Abstract

Peptides containing an α-azanorvaline residue at the C-terminus and N-[(1-methoxycarbonylalkyl)carbamoyl] group at the N-terminus have been made as inhibitors of human leucocyte elastase. A number of analogues with an amide bond replaced by a thiomethylene group have also been prepared. The analogues were tested against leucocyte elastase using MeO-Suc-Ala-Ala-Pro-Val-p-nitroanilide as a substrate and the results were obtained as IC₅₀ values. Both types of analogues inhibited the leucocyte elastase; the most potent of these was N-[(1-methoxycarbonylbutyl)carbamoyl]-L-valyl-L-prolyl-α-azanorvaline phenyl ester (2)(IC₅₀, 0.28 µM, K_i 0.02 µM).