Proteinase inhibitors. 1. Inhibitors of elastase

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Abstract
A series of peptides and depsipeptides containing 2-methylcarbazic acid (H-Mec-OH), the 2-aza analogue of alanine, was prepared and tested as inhibitors of pancreatic [hog] and human granulocyte elastases. A requirement for a minimum chain length and specific amino acid sequence was observed which correlates well with substrate and inhibitor studies by others in this field. The most active inhibitors have the structure Ac-Ala-Ala-Pro-Mec-Lac-R. When Lac-R is an ester, only the pancreatic enzyme is inhibited. When Lac-R is an amide or hydrazide, then both enzymes are inhibited. Inhibitory activity is reversible; inhibitors are not hydrolyzed by the enzyme, and inhibition is noncompetitive with synthetic substrates of similar structure, suggesting that binding at sites adjacent to the carboxyl group of the amino acid analogue, 2-methylcarbazic acid, is important for this inhibition. Differences between pancreatic and granulocyte elastases are demonstrated.

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