HIV-1 Fusion Inhibitor Peptides Enfuvirtide and T-1249 Interact with Erythrocyte and Lymphocyte Membranes

被引:43
|
作者
Matos, Pedro M. [1 ]
Castanho, Miguel A. R. B. [1 ]
Santos, Nuno C. [1 ]
机构
[1] Univ Lisbon, Fac Med, Inst Mol Med, P-1200 Lisbon, Portugal
来源
PLOS ONE | 2010年 / 5卷 / 03期
关键词
MULTIFUNCTIONAL DOMAINS; GP41; CELLS; ENTRY; BIOMEMBRANES; MECHANISMS; FLUIDITY; RECEPTOR; BINDING; AIDS;
D O I
10.1371/journal.pone.0009830
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Enfuvirtide and T-1249 are two HIV-1 fusion inhibitor peptides that bind to gp41 and prevent its fusogenic conformation, inhibiting viral entry into host cells. Previous studies established the relative preferences of these peptides for membrane model systems of defined lipid compositions. We aimed to understand the interaction of these peptides with the membranes of erythrocytes and peripheral blood mononuclear cells. The peptide behavior toward cell membranes was followed by di-8-ANEPPS fluorescence, a lipophilic probe sensitive to the changes in membrane dipole potential. We observed a fusion inhibitor concentration-dependent decrease on the membrane dipole potential. Quantitative analysis showed that T-1249 has an approximately eight-fold higher affinity towards cells, when compared with enfuvirtide. We also compared the binding towards di-8-ANEPPS labeled lipid vesicles that model cell membranes and obtained concordant results. We demonstrated the distinct enfuvirtide and T-1249 membranotropism for circulating blood cells, which can be translated to a feasible in vivo scenario. The enhanced interaction of T-1249 with cell membranes correlates with its higher efficacy, as it can increase and accelerate the drug binding to gp41 in its pre-fusion state.
引用
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页数:8
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