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dc.creatorLomonte, Bruno
dc.creatorPizarro Cerdá, Javier
dc.creatorAngulo Ugalde, Yamileth
dc.creatorGorvel, Jean Pierre
dc.creatorMoreno Robles, Edgardo
dc.date.accessioned2017-12-01T19:28:14Z
dc.date.available2017-12-01T19:28:14Z
dc.date.issued1999
dc.identifier.citationhttp://www.sciencedirect.com/science/article/pii/S0005273699001431es_ES
dc.identifier.issn0005-2736
dc.identifier.urihttp://hdl.handle.net/10669/73485
dc.description.abstractMyotoxin II is a group II Lys49 phospholipase A2 (PLA2) isolated from the venom of the snake Bothrops asper. Previous studies on a synthetic peptide derived from its heparin-binding, cationic/hydrophobic sequence 115^129 demonstrated a direct functional role of this particular region in the in vitro cytolytic and bactericidal actions of the protein. Nevertheless, no significant myonecrosis has been observed after local intramuscular injection of peptide 115-129 (p115-129) in mice. Since the membrane-damaging action of p115-129 was proposed to depend on its amphiphilic character, the present study examined the effects of substituting its cluster of three tyrosine residues by tryptophan residues, on its toxic/pharmacological activities in vitro and in vivo. This substitution resulted in a drastic enhancement of the membrane-damaging activities of the peptide (p115-W3), together with the clear expression of myotoxic activity in vivo. Both the heparin-binding and antigenic characteristics of p115-129 were essentially conserved in p115-W3, suggesting that the modification did not lead to radical structural alterations. In addition to myotoxicity, cytotoxicity, and bactericidal action, p115-W3 exerted edema-forming activity in the mouse footpad assay. Thus, the synthetic 13-mer p115-W3 reproduced all the known toxic effects of myotoxin II. In spite of its potent membrane-damaging actions, p115-W3 did not acquire direct hemolytic activity upon mouse erythrocytes, an effect which is not present in myotoxin II, but that has been ascribed to the presence of tryptophan in other cationic, membrane-damaging peptides such as mellitin from bee venom. The myotoxic activity of p115-W3 herein described constitutes the first example of a short, PLA2-based linear synthetic peptide with the ability to reproduce this effect of a parent protein in vivo. This finding is in clear support of the proposed relevance of the C-terminal region 115^129 in all the membrane-damaging mechanisms exerted by myotoxin II, including the myotoxic mechanism.es_ES
dc.description.sponsorshipVicerrectorı́a de Investigación, Universidad de Costa Rica/[VI-741-95-264]/UCR/Costa Ricaes_ES
dc.description.sponsorshipVicerrectorı́a de Investigación, Universidad de Costa Rica/[VI-741-96-265]/UCR/Costa Ricaes_ES
dc.description.sponsorshipInternational Foundation for Science/[F/1388-3F]/IFS/Costa Ricaes_ES
dc.description.sponsorshipInternational Foundation for Science/[F/2766-1]/IFS/Costa Ricaes_ES
dc.description.sponsorshipConsejo Nacional para Investigaciones Cientı́ficas y Tecnológicas/[98-013-FO]/CONICIT/Costa Rica,es_ES
dc.description.sponsorshipCR-USA Foundation/[R-21599]//Costa Ricaes_ES
dc.description.sponsorshipNeTropica Program/[6-3-99]//Costa Ricaes_ES
dc.language.isoen_USes_ES
dc.sourceBiochimica et Biophysica, Vol. 1461 (1), pp. 19-26.es_ES
dc.subjectMyotoxines_ES
dc.subjectBothrops asperes_ES
dc.subjectSnake venomes_ES
dc.titleTyr→Trp-substituted peptide 115-129 of a Lys49 phospholipase A2 expresses enhanced membrane-damaging activities and reproduces its in vivo myotoxic effectes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.identifier.doi10.1016/S0005-2736(99)00143-1
dc.description.procedenceUCR::Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)es_ES
dc.description.procedenceUCR::Docencia::Salud::Facultad de Medicina:: Escuela de Medicinaes_ES


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