Phosphinic pseudo-tripeptides as potent inhibitors of matrix metalloproteinases:: A structure-activity study

被引：108

作者：

Vassiliou, S

Mucha, A

Cuniasse, P

Georgiadis, D

Lucet-Levannier, K

Beau, F

Kannan, R

Murphy, G

Knäuper, V

Rio, MC

Basset, P

Yiotakis, A

Dive, V ^{[1
]}

机构：

[1] CEA, Dept Ingn & Etud Prot, F-91191 Gif Sur Yvette, France

[2] Univ Athens, Dept Chem, Organ Chem Lab, Athens, Greece

[3] Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England

[4] Univ Strasbourg 1, CNRS, INSERM, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France

[5] Wroclaw Tech Univ, Inst Organ Chem Biochem & Biotechnol, PL-50370 Wroclaw, Poland

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1999年 / 42卷 / 14期

关键词：

D O I：

10.1021/jm9900164

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Several phosphinic pseudo-tripeptides of general formula R-Xaa Psi (PO2-CH2)Xaa'-Yaa'-NH2 were synthesized and evaluated for their in vitro activities to inhibit stromelysin-3, gelatinases A and B, membrane type-1 matrix metalloproteinase, collagenases 1 and 2, and matrilysin. With the exception of collagenase-1 and matrilysin, phosphinic pseudo-tripeptides behave as highly potent inhibitors of matrix metalloproteinases, provided they contain in P-1' position an unusual long aryl-alkyl substituent. Study of structure-activity relationships regarding the influence of the R and Xaa' substituents in this series may contribute to the design of inhibitors able to block only a few members of the matrix metalloproteinase family.

引用

页码：2610 / 2620

页数：11

共 48 条

[41] Characterization of structural determinants and molecular mechanisms involved in pro-stromelysin-3 activation by 4-aminophenylmercuric acetate and furin-type convertases [J].