DESIGN OF (OMEGA-N-(O-ACYL)HYDROXY AMID) AMINODICARBOXYLIC ACID PYRROLIDIDES AS POTENT INHIBITORS OF PROLINE-SPECIFIC PEPTIDASES

被引：29

作者：

DEMUTH, HU ^{[1
]}

SCHLENZIG, D ^{[1
]}

SCHIERHORN, A ^{[1
]}

GROSCHE, G ^{[1
]}

CHAPOTCHARTIER, MP ^{[1
]}

GRIPON, JC ^{[1
]}

机构：

[1] INRA,STN RECH LAITIERES,UNITE ENZYMOL,F-78352 JOUY EN JOSAS,FRANCE

来源：

FEBS LETTERS | 1993年 / 320卷 / 01期

关键词：

PROLYL ENDOPEPTIDASE; DIPEPTIDYL PEPTIDASE-IV; INHIBITION; PYRROLIDIDE;

D O I：

10.1016/0014-5793(93)81649-K

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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(i) values in the muM range. Boc-protected (omega-N-hydroxy acyl amid) aminodiacarboxylic acid pyrrolidides inhibit substrate hydrolysis by prolyl endopeptidases from different sources competitively reaching K(i) values of 30 nM to 60 muM. Additionally, alpha-N-BOC-(omega-N-hydroxy acetyl) glutaminyl pyrrolidide modifies human placenta prolyl endopeptidase in a time-dependent reaction.

引用

页码：23 / 27

页数：5

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