title: Identification of new snake venom metalloproteinase inhibitors using compound screening and rational Peptide design.
abstract: 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.
authors.affiliation: Escuela de Química, Universidad de Costa Rica , San José, Costa Rica ; Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica , San José, Costa Rica.
authors.forename: Fabián
authors.initials: F
authors.lastname: Villalta-Romero
authors.affiliation: Centro de Investigación Príncipe Felipe , E-46012 Valencia, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Gortat
authors.affiliation: Centro de Investigación Príncipe Felipe , E-46012 Valencia, Spain.
authors.forename: Andrés E
authors.initials: AE
authors.lastname: Herrera
authors.affiliation: Escuela de Química, Universidad de Costa Rica , San José, Costa Rica.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Arguedas
authors.affiliation: Escuela de Química, Universidad de Costa Rica , San José, Costa Rica.
authors.forename: Javier
authors.initials: J
authors.lastname: Quesada
authors.affiliation: Center for Applied Toxinology, Instituto Butantan , Sao Paulo, Brazil.
authors.forename: Robson Lopes
authors.initials: RL
authors.lastname: de Melo
authors.affiliation: Instituto de Biomedicina , IBV-CSIC, E-46010 Valencia, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Calvete
authors.affiliation: Escuela de Química, Universidad de Costa Rica , San José, Costa Rica.
authors.forename: Mavis
authors.initials: M
authors.lastname: Montero
authors.affiliation: Escuela de Química, Universidad de Costa Rica , San José, Costa Rica.
authors.forename: Renato
authors.initials: R
authors.lastname: Murillo
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica , San José, Costa Rica.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rucavado
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica , San José, Costa Rica.
authors.forename: José María
authors.initials: JM
authors.lastname: Gutiérrez
authors.affiliation: Centro de Investigación Príncipe Felipe , E-46012 Valencia, Spain ; Instituto de Biomedicina , IBV-CSIC, E-46010 Valencia, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Pérez-Payá
keywords: BaP1; metalloproteinase inhibitors; protein docking; snake venom metalloproteinases