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Benzamido-l-aminocyclopropylcarbonyl-phenylalanine and -proline are shown to be irreversible inhibitors of carboxypeptidase A by a mechanism probably involving glutamate-270 as a nucleophile.The rational design of drugs based upon enzyme inhibitors has been greatly advanced by taking advantage of the mechanism of action of the enzyme to generate a locally reactive group.1The reactivity of the cyclopropane group has been harnessed for enzyme inhibition by radical ring opening,* nucleophilic addition to cyclopropanones,3 and in our studies, nucleophilic ring opening of cyclopropanes substituted with electron withdrawing groups.4 Small groups such as cyclopropanes can be incorporated into substrate analogues for many enzymes and the transposability of such latent reactive groups is an attractive strategy for the design of enzyme inhibitors. Having established that cyclopropane derivatives are latent inhibitors of alcohol dehydrogenase and lactate dehydrogenase4.5

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Latent Inhibitors. Part 9. Substrate Activated Time-Dependent Inhibition of Carboxypeptidase A by Aminocyclopropanecarboxylic Acid Derivatives and Analogues -(kinetics; mechanisms). -(KEMP, A.; NER, S. K.; REES, L.; SUCKLING, C. J.; TEDFORD, M. C.; BELL, A. R.; WRIGGLESWORTH, R.; J. Chem. Soc., Perkin Trans. II (1993) 4, 741-748; Dep. Pure Appl. Chem., Univ. Strathclyde, Glasgow G1 1XL, UK; EN)

The putrescines (I) are oxidized in the presence of diamine oxidases from pea seedlings or pig kidney to give the aldehydes (II).