Design of (ω-N-(O-acyl)hydroxy amid) aminodicarboxylic acid pyrrolidides as potent inhibitors of proline-specific peptidases
Open Access
- 29 March 1993
- journal article
- Published by Wiley in FEBS Letters
- Vol. 320 (1) , 23-27
- https://doi.org/10.1016/0014-5793(93)81649-k
Abstract
A novel class of competitive, acylating inhibitors for the proline‐specific peptidases: dipeptidyl peptidase IV, dipeptidyl peptidase II and prolyl endopeptidase, has been developed. The inhibitor molecules combine the efficacy of aminoacyl pyrrolidides and the potential transacylating capability of diacyl hydroxyl amines. The N‐terminal deblocked inhibitors are potent reversible inhibitors of porcine kidney dipeptidyl peptidase IV, human placenta dipeptidyl peptidase II exhibiting K 1 values in the μM range. Boc‐protected (ω‐N‐hydroxy acyl amid) aminodiacarboxylic acid pyrrolidides inhibit substrate hydrolysis by prolyl endopeptidases from different sources competitively reaching K, values of 30 nM to 60 μM. Additionally, α‐N‐BOC‐(ω‐N‐hydroxy acetyl) glutaminyl pyrrolidide modifies human placenta prolyl endopeptidase in a time‐dependent reaction.Keywords
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