Investigating the effect of different positioning of lysine residues along the peptide chain of mastoparans for their secondary structures and biological activities

Autor(es)

de Souza, Bibiana Monson ^[1] ; dos Santos Cabrera, Marcia Perez ^[2] ; Ruggiero Neto, Joao ^[2] ; Palma, Mario Sergio ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, UNESP, Inst Biosci Rio Claro, CEIS Dept Biol, BR-13506900 Rio Claro, SP - Brazil

^[2] UNESP, IBILCE, Dept Phys, Sao Jose Do Rio Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Amino Acids; v. 40, n. 1, p. 77-90, JAN 2011.
• Citações Web of Science: 18

Resumo

In order to investigate the effect of the different positions of the positive charges generated by the ionization of the side-chain of lysine residues, on the structure-activity relationship of the mastoparans, the peptides Protonectarina-MP (INWKALLDAAKKVL-NH2), Parapolybia-MP (INWKKMAATALKMI-NH2) and Asn-2-Polybia-MP I (INWKKLLDAAKQIL-NH2) and MK-578 (INWLKAKKVAGMIL-NH2) were investigated as models. Thus, the four peptides had their secondary structure studied and were submitted to assays of mast cell degranulation, hemolysis, and antibiosis. The results of the bioassays made clear that those peptides bearing the positive charges positioned at the positions 4/5 and/or from 11 to 13 are the most active ones; meanwhile, the localization of the positive charges in the middle of peptide chain resulted in a poorly active peptide. Thus, Protonectarina-MP, Parapolybia-MP, and Asn-2-Polybia-MP I presented physiologically important hemolysis and antibiosis, while MK-578 presented only a reduced antibiotic activity. Circular dichroism analysis were carried-out in different environments revealing that the anionic environment of a mixture of phosphatidylcholine and phosphatidylglycerol (70:30) liposomes favored the higher helical content of the four peptides in this study in relation to the zwiterionic environment of 100% phosphatidylcholine liposomes. The positioning of the lysine residues at the strategic positions (4/5 and 11-13), flanking and maintaining stable alpha-helix which extends from the 4th to the 13th residue along the peptide chain, seems to contribute to maximal lytic efficiency of the mastoparans, which in turn results in a more homogeneous hydrophobic surface in the amphipathic structure. (AU)

• Processo FAPESP: 04/07942-2 - A bioprospecção da fauna de artrópodes do estado de São Paulo pela procura de compostos-líderes para o desenvolvimento racional de novos fármacos e pesticidas seletivos
• Beneficiário: Mario Sergio Palma
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular