Steinmetzer T, Silberring J, Mrestani-Klaus C, Fittkau S, Barth A, Demuth H U
Department of Biochemistry, Martin-Luther-University of Halle, Saale, Germany.
J Enzyme Inhib. 1993;7(2):77-85. doi: 10.3109/14756369309040750.
Prolyl endopeptidase (PEP) and dipeptidyl peptidase IV (DP IV) are serine enzymes cleaving highly specific prolyl peptide bonds. Both enzymes were found to be inhibited by newly designed peptidyl ammonium and pyridinium methyl ketones acting as slow binding inhibitors. The most potent inhibitor of PEP is Z-Pro-Pro-CH2N+C5H5 exhibiting a Ki* value of 1.8 nM with a first-order rate constant of Kon 0.0022 s-1 for the formation of the tight enzyme-inhibitor complex. DP IV and H-Pro-Pro-CH2N+ (CH3)3 form an enzyme-inhibitor-complex with an apparent second order rate constant of 2713 M-1 s-1. In contrast to the very stable N-terminal protected Z-Pro-Pro-CH2N+ (CH3)3, the deblocked derivative decomposes rapidly in aqueous solution.
脯氨酰内肽酶（PEP）和二肽基肽酶IV（DP IV）是切割高度特异性脯氨酰肽键的丝氨酸酶。发现这两种酶都受到新设计的肽基铵和吡啶鎓甲基酮的抑制，这些化合物作为慢结合抑制剂起作用。PEP最有效的抑制剂是Z-Pro-Pro-CH2N+C5H5，其Ki*值为1.8 nM，形成紧密酶-抑制剂复合物的一级速率常数Kon为0.0022 s-1。DP IV和H-Pro-Pro-CH2N+(CH3)3形成酶-抑制剂复合物，表观二级速率常数为2713 M-1 s-1。与非常稳定的N端保护的Z-Pro-Pro-CH2N+(CH3)3不同，去保护的衍生物在水溶液中迅速分解。
