Integrin inhibitors from snake venom: Exploring the relationship between the structure and activity of RGD-peptides

Integrin inhibitors from snake venom: Exploring the relationship between the structure and activity of RGD-peptides

Autor Wermelinger, Luciana Serrão Google Scholar
Geraldo, Reinaldo Barros Google Scholar
Frattani, Flavia Serra Google Scholar
Rodrigues, Carlos Rangel Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Castro, Helena Carla Google Scholar
Zingali, Russolina Benedeta Google Scholar
Instituição Universidade Federal Fluminense (UFF)
Universidade Federal do Rio de Janeiro (UFRJ)
Universidade Federal de São Paulo (UNIFESP)
Resumo alpha IIb beta 3 is ail integrin that is involved in platelet adhesion and aggregation. This receptor may be inhibited by cysteine-rich peptides known as disintegrins. We isolated two disintegrins from Bothrops jararaca venom called jarastatin and jararacin. We evaluated the structural characteristics and the effects on human platelet aggregation of these disintegrins. Inhibitory profiles were compared to six distinct peptides synthesized based on their RGD hairpin loop primary sequences. Both jarastatin and jararacin inhibited ADP and thrombin induction. Conversely, none of the cyclic peptides showed high-quality activity in assays induced by ADP or thrombin. We constructed homology models for all of these molecules, and theoretically evaluated their interaction with the alpha IIb beta 3 crystal structure using a molecular modeling approach. These results Support the observations that the cyclic peptides had little effects, and also reinforce the observation that residues outside the disintegrin RGD sequence are required for interactions with receptor. (c) 2008 Elsevier Inc. All rights reserved.
Assunto Disintegrin
Aggregation
Receptor
Platelet
Inhibitor
RGD-peptide
Integrin
Jarastatin
Jararacin
Molecular modeling
Idioma Inglês
Financiador Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Universidade Federal Fluminense (UFF) (Brazil)
Data 2009-02-01
Publicado em Archives of Biochemistry and Biophysics. New York: Elsevier B.V., v. 482, n. 1-2, p. 25-32, 2009.
ISSN 0003-9861 (Sherpa/Romeo, fator de impacto)
Editor Elsevier B.V.
Extensão 25-32
Fonte http://dx.doi.org/10.1016/j.abb.2008.11.023
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000263388100004
URI http://repositorio.unifesp.br/handle/11600/31287

Mostrar registro completo




Arquivos deste item

Arquivos Tamanho Formato Visualização

Não existem arquivos associados a este item.

Este item aparece na(s) seguinte(s) coleção(s)