Identification of New Snake Venom Metalloproteinase Inhibitors Using Compound Screening and Rational Peptide Design
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- 作者：Fabi谩n Villalta-Romero ; Anna Gortat ; Andr茅s E. Herrera ; Rebeca Arguedas ; Javier Quesada ; Robson Lopes de Melo ; Juan J. Calvete ; Mavis Montero ; Renato Murillo ; Alexandra Rucavado ; Jos茅 Mar铆a Guti茅rrez ; Enrique P茅rez-Pay谩
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：July 12, 2012
- 年：2012
- 卷：3
- 期：7
- 页码：540-543
- 全文大小：246K
- 年卷期：v.3,no.7(July 12, 2012)
- ISSN：1948-5875
文摘
The majority of snakebite envenomations in Central America are caused by the viperid species Bothrops asper, whose venom contains a high proportion of zinc-dependent metalloproteinases that play a relevant role in the pathogenesis of hemorrhage characteristic of these envenomations. Broad metalloproteinase inhibitors, such as the peptidomimetic hydroxamate Batimastat, have been shown to inhibit snake venom metalloproteinases (SVMP). However, the difficulty in having open public access to Batimastat and similar molecules highlights the need to design new inhibitors of SVMPs that could be applied in the treatment of snakebite envenomations. We have chosen the SVMP BaP1 as a model to search for new inhibitors using different strategies, that is, screening of the Prestwick Chemical Library and rational peptide design. Results from these approaches provide clues on the structural requirements for efficient BaP1 inhibition and pave the way for the design of new inhibitors of SVMP.