Inhibition of adamalysin II and MMPs by phosphonate analogues of snake venom peptides

被引：23

作者：

D'Alessio, S

Gallina, C

Gavuzzo, E

Giordano, C

Gorini, B

Mazza, F

Paradisi, MP

Panini, G

Pochetti, G

Sella, A

机构：

[1] Polifarma Res Ctr, I-00185 Rome, Italy

[2] Univ G DAnnunzio, Ist Sci Farm, I-66100 Chieti, Italy

[3] CNR, Ist Strutturist Chim, I-00016 Monterotondo, Italy

[4] Univ Rome La Sapienza, CNR, Ctr Studio Chim Farm, I-00185 Rome, Italy

[5] Univ Aquila, Dipartimento Chim Ingn Chim & Mat, I-67010 Laquila, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 1999年 / 7卷 / 02期

关键词：

retrobinding pseudopeptide inhibitors; adamalysin II; matrix metalloproteinases;

D O I：

10.1016/S0968-0896(98)00243-0

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：

Phosphonate analogues of the peptidomimetic N-(Furan-2-yl)carbonyl-Leu-Trp-OH were prepared with the goal of evaluating the effect of phosphonate for carboxylate replacement on binding with snake venom metalloproteinases and MMPs, N(Furan-2-yl)carbonyl-Leu-L-Trp(P)-(OH)(2) showed a 75-fold increase of the inhibiting activity against adamalysin II, a snake venom metalloproteinase structurally related to MMPs and TACE. Both the phosphonate and carboxylate peptidomimetics fit into the active site adopting a retrobinding mode and provide the structural base for a new class of metalloproteinases inhibitors. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：389 / 394

页数：6

共 27 条

[1]

[Anonymous], COMMUNICATION

[2] Molecular recognition of protein-ligand complexes: Applications to drug design [J].