Hb40-61a: Novel analogues help expanding the knowledge on chemistry, properties and candidacidal action of this bovine alpha-hemoglobin-derived peptide

Autor(es)

Carvalho, L. A. C. ^[1] ; Remuzgo, C. ^[2] ; Perez, K. R. ^[3] ; Machini, M. T. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil

^[2] Butantan Inst, Special Lab Pain & Signaling, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES; v. 1848, n. 12, p. 3140-3149, DEC 2015.
• Citações Web of Science: 3

Resumo

This study expands the knowledge on chemical synthesis and properties of Hb40-61a as well as provides results of the first steps given towards knowing how it kills Candida cells. For the first time, this peptide, its all-D analogue (D-Hb40-61a) and its fluorescently labeled analogue (FAM-Hb40-61a) were successfully assembled on resin at 60 degrees C using conventional heating in all steps. Purified and characterized, these peptides exhibited very low toxicity on human erythrocytes. Hb40-61a and D-Hb40-61a were equally active against Candida strains, ruling out sterically specific interactions on their working mechanism. Cell permeabilization assays confirmed progressive damage of the yeast plasma membrane with increasing concentrations of Hb40-61a. While experiment using the fluorescent probe DiBAC4(5) revealed that this synthetic hemocidin alters the yeast plasma membrane potential, test employing DPH indicated that Hb40-61 a might affect its dynamics. Exposure of the yeast cells to FAM-Hb40-61a showed that the peptide accumulates in the cell membrane at the 1/2 MIC, but stains about 97% of the cells at the MIC. Such effect is salt-dependent and partially energy-dependent. These new findings indicate that the central target of Hb40-61a in Candida cells is the plasma membrane and that this synthetic hemocidin should be considered as a potential candidacidal for topic uses. (C) 2015 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 08/11695-1 - Tecnologias alternativas na química de peptídeos: solvólise mediada por íons metálicos, biocatálise, aquecimento convencional e microondas
• Beneficiário: Maria Teresa Machini
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/09068-4 - Microondas, biocatálise, íons metálicos divalentes e nanotecnologia na síntese de peptídeos
• Beneficiário: Maria Teresa Machini
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 00/11624-5 - Embriologia de Gastropoda: análise em microscopia de varredura laser confocal
• Beneficiário: Toshie Kawano
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários