N-hydroxyurea as zinc binding group in matrix metalloproteinase inhibition:: Mode of binding in a complex with MMP-8

被引：48

作者：

Campestre, C

Agamennone, M

Tortorella, P

Preziuso, S

Biasone, A

Gavuzzo, E

Pochetti, G

Mazza, F

Hiller, O

Tschesche, H

Consalvi, V

Gallina, C ^{[1
]}

机构：

[1] Univ G DAnnunzio, Dipartimento Sci Farm, Chieti, Italy

[2] CNR, Ist Cristallog, Rome, Italy

[3] Univ Aquila, Dipartimento Chim Ingn Chim & Mat, I-67100 Laquila, Italy

[4] Univ Bielefeld, Fac Chem, D-4800 Bielefeld, Germany

[5] Univ Roma La Sapienza, Dipartimento Sci Biochim, Rome, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 01期

关键词：

MMPs inhibitors; zinc binding groups; N-hydroxyurea mode of binding; N-hydroxyurea inhibitors; X-ray crystal structure; molecular modeling;

D O I：

10.1016/j.bmcl.2005.09.057

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The first crystallographic structure of an N-hydroxyurea inhibitor bound into the active site of a matrix metalloproteinase is reported. The ligand and three other analogues were prepared and studied as inhibitors of MMP-2, MMP-3, and MMP-8. The crystal structure of the complex with MMP-8 shows that the N-hydroxyurea, contrary to the analogous hydroxamate, binds the catalytic zinc ion in a monodentate rather than bidentate mode and with high out-of-plane distortion of the amide bonds. (c) 2005 Elsevier Ltd. All rights reserved.

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页码：20 / 24

页数：5

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