TY - JOUR
T1 - Latent inhibitors. Part 9.
T2 - substrate activated time-dependent inhibition of carboxypeptidase a by aminocyclopropanecarboxylic acid derivatives and analogues
AU - Kemp, Alison
AU - Ner, Surjit K.
AU - Rees, Lilias
AU - Suckling, Colin J.
AU - Tedford, M. Catriona
AU - Bell, Andrew R.
AU - Wrigglesworth, Roger
PY - 1993/4
Y1 - 1993/4
N2 - 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.
AB - 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.
U2 - 10.1039/P29930000741
DO - 10.1039/P29930000741
M3 - Article
SN - 1472-779X
VL - 1993
SP - 741
EP - 748
JO - Journal of the Chemical Society, Perkin Transactions 2
JF - Journal of the Chemical Society, Perkin Transactions 2
IS - 4
ER -