A series of 1-aminocyclopropanecarboxylic acid derivatives and analogues have been synthesised as potential inhibitors of carboxypeptidase A. Whereas simple cyclopropylcarboxamido derivatives of Gly, Phe and Pro showed no indications of time-dependent, irreversible inhibition, benzamido-1-aminocyclopropane carboxamido-Phe and Pro were characterised as latent inhibitors. The former was also a substrate for carboxypeptidase A but the latter was purely an inhibitor. This behaviour suggested that cyclopropylketones should also be inhibitors of carboxypeptidase A; this suggestion was confirmed experimentally. Kinetic experiments showed surprisingly that the rate of inhibition is increased in the presence of substrate, hippurylphenylalanine. Related secondary alcohols also acted as time-dependent inhibitors. The results are evaluated in the context of current views on the mechanism of action of carboxypeptidase A.
|Number of pages||8|
|Journal||Journal of the Chemical Society, Perkin Transactions 2|
|Publication status||Published - Apr 1993|
Kemp, A., Ner, S. K., Rees, L., Suckling, C. J., Tedford, M. C., Bell, A. R., & Wrigglesworth, R. (1993). Latent inhibitors. Part 9. substrate activated time-dependent inhibition of carboxypeptidase a by aminocyclopropanecarboxylic acid derivatives and analogues. Journal of the Chemical Society, Perkin Transactions 2, 1993(4), 741-748. https://doi.org/10.1039/P29930000741