Inhibitors of pancreatic and leukocyte elastase
The following alkylamides of ω-carboxyalkanoyldi- and tripeptides of the Ala-Pro or Ala-Ala-Pro sequence have been prepared: ethylamide-, propylamide-, and isobutylamide of 3-carboxypropionylalanyl-proline, ethylamide of 3-carboxypropionylalanyl-alanyl-proline and ethylamide-, propylamide, and isobutylamide of 4-carboxybutyrylalanyl-alanyl-proline. The inhibitors were synthesized by fragment condensation in solution or by gradual construction. The inhibition constants Ki were determined by means of pancreatic elastase (substrates - p-nitroanilides of 4-carboxybutyrylalanyl-alanyl-alanyl-alanine and 3-carboxypropionylalanyl-alanyl-alanyl-alanine) and leukocyte elastase (substrate - p-nitroanilide of 4-carboxybutyrylalanyl-alanyl-alanyl-valine). The strongest inhibitions (Ki) were recorded in ethylamide of 4-carboxybutyrylalanyl-alanyl-proline, 2.0 and 1.6 μmol l-1 for pancreatic elastase, and in propylamide of 4-carboxybutyrylalanyl-alanyl-proline, 0.4 mmol l-1 for leukocyte elastase.
Amino acids and peptides. XXX. Synthesis of eglin c(41-49) and eglin c(60-63) and examination of their inhibitory activity towards human leukocyte elastase, cathepsin G, porcine pancreatic elastase and .ALPHA.-chymotrypsin.
