Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/6751
Título: Unravelling the molecular basis of the selectivity of the HIV-1 fusion inhibitor sifuvirtide towards phosphatidylcholine-rich rigid membranes
Autor: Franquelim, Henri G.
Veiga, A. Salomé
Weissmüller, G.
Santos, Nuno C.
Castanho, Miguel A. R. B.
Palavras-chave: HIV
Fusion inhibitor
Peptide
Membrane
Gel phase phosphatidylcholine
Data: 2010
Editora: Elsevier
Citação: Biochimica et Biophysica Acta 1798 (2010) 1234–1243
Resumo: Sifuvirtide, a 36 amino acid negatively charged peptide, is a novel HIV-1 fusion inhibitor with improved antiretroviral activity. In this work we evaluated the physical chemistry foundation of the interaction of sifuvirtide with biomembrane model systems. Since this peptide has aromatic residues, fluorescence spectroscopy techniques were mostly used. The interaction was assessed by partition and quenching experiments. Results showed no significant interaction with large unilamellar vesicles composed by sphingomyelin and ceramide. In contrast, sifuvirtide presented selectivity towards vesicles composed by phosphatidylcholines (PC) in the gel phase, in opposition to fluid phase PC vesicles. The interaction of this peptide with gel phase PC membranes (Kp=1.2×10/2) is dependent on the ionic strength, which indicates the mediation of electrostatic interactions at an interfacial level. The effects of sifuvirtide on the lipid membranes' structural properties were further evaluated using dipole-potential membrane probes, zetapotential, dynamic light scattering and atomic force microscopy measurements. The results show that sifuvirtide does not cause a noticeable effect on lipid bilayer structure, except for membranes composed by cationic phospholipids. Altogether, we can conclude that sifuvirtide presents a specific affinity towards rigid PC membranes, and the interaction is mediated by electrostatic factors, not affecting the membrane architecture.
Descrição: © 2010 Elsevier B.V. All rights reserved
Peer review: yes
URI: http://dx.doi.org/10.1016/j.bbamem.2010.02.010
http://hdl.handle.net/10451/6751
ISSN: 0006-3002
Versão do Editor: Supplementary data associated with this article can be found, in the online version
Aparece nas colecções:IMM - Artigos em Revistas Internacionais

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