Jan Ten Broeke

Inhibition of thermolysin by N-carboxymethyl dipeptides

Abstract A design principle effective for generating inhibitors of angiotensin converting enzyme has been successfully extended to inhibitors of another Zn ++ endopeptidase, thermolysin. Hence, N-(1-carboxy-3-phenylpropyl)LeuTrp is found to be a potent inhibitor of thermolysin, K i ∼ 5 × 10 −8 M.

Inhibition of procine kidney “enkephalinase” by substituted-N-carboxymethyl dipeptides

Abstract A design effective for generating inhibitors of angiotensin converting enzyme has been successfully extended to inhibitors of another Zn ++ peptidase. A series of potent inhibitors for the zinc metalloendopeptidase associated with porcine kidney microsomes has been developed. Most contain the (S)-N-(1-carboxy-3-phenylpropyl)-L-Phe-X backbone. The most effective inhibitors with ID 50 values in the 10 −7 M range at pH 7.5 and 22°C were those where X = glycine, β-alanine, γ-amino butyric acid. A simple nomenclature designating substituted N-carboxy-methyl amino acid derivatives as -[N]- sharing amino acid derivatives is described.