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• W2588731569 endingPage "e0171567" @default.
• W2588731569 startingPage "e0171567" @default.
• W2588731569 abstract "Most mechanistic studies on human immunodeficiency virus (HIV) peptide fusion inhibitors have focused on the interactions between fusion inhibitors and viral envelope proteins. However, the interactions of fusion inhibitors with viral membranes are also essential for the efficacy of these drugs. Here, we utilized surface plasmon resonance (SPR) technology to study the interactions between the HIV fusion inhibitor peptides sifuvirtide and enfuvirtide and biomembrane models. Sifuvirtide presented selectivity toward biomembrane models composed of saturated dipalmitoylphosphatidylcholine (DPPC) (32-fold higher compared with unsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine [POPC]) and sphingomyelin (SM) (31-fold higher compared with POPC), which are rigid compositions enriched in the HIV viral membrane. In contrast, enfuvirtide showed no significant selectively toward these rigid membrane models. Furthermore, the bindings of sifuvirtide and enfuvirtide to SM bilayers were markedly higher than those to monolayers (14-fold and 23-fold, respectively), indicating that the inner leaflet influences the binding of these drugs to SM bilayers. No obvious differences were noted in the bindings of either peptide to the other mono- and bilayer models tested, illustrating that both peptides interact with these membranes through surface-binding. The bindings of the inhibitor peptides to biomembranes were found to be driven predominantly by hydrophobic interactions rather than electrostatic interactions, as determined by comparing their affinities to those of positively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine (EPC) to zwitterionic membrane models. The improved efficiency of sifuvirtide relative to enfuvirtide might be related to its ability to adsorb on rigid lipidic areas, such as the viral envelope and lipid rafts, which results in an increased sifuvirtide concentration at the fusion site." @default.
• W2588731569 created "2017-02-24" @default.
• W2588731569 creator A5037651553 @default.
• W2588731569 creator A5048712863 @default.
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• W2588731569 date "2017-02-16" @default.
• W2588731569 modified "2023-10-10" @default.
• W2588731569 title "The improved efficacy of Sifuvirtide compared with enfuvirtide might be related to its selectivity for the rigid biomembrane, as determined through surface plasmon resonance" @default.
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• W2588731569 doi "https://doi.org/10.1371/journal.pone.0171567" @default.
• W2588731569 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5312942" @default.
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• W2588731569 hasPublicationYear "2017" @default.
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