PHOSPHOLIPID INTERACTIONS OF SYNTHETIC PEPTIDES REPRESENTING THE N-TERMINUS OF HIV GP41

Peptides representing the N-terminal 23 residues of the surface protein gp41 of LAVla and LAVmal strains of the human immunodeficiency virus were synthesized and their interactions with phospholipid vesicles studied. The peptides are surface-active and penetrate lipid monolayers composed of negatively charged but not neutral lipids. Similarly, the peptides induce lipid mixing and solute (6-carboxyfluorescein) leakage of negatively charged, but not neutral, vesicles. Circular dichroism and infrared spectroscopy show that at low peptide:lipid ratios (approximately 1:200), the peptides bind to negatively charged vesicles as α-helices. At higher peptide:lipid ratios (1:30), a ß conformation is observed for the LAV1a peptide, accompanied by a large increase in light scattering. The LAVmal peptide showed less β-structure and induced less light scattering. With neutral vesicles, only the ß conformation and a peptide:lipid ratio-dependent increase in vesicle suspension light scattering were observed for both peptides. We hypothesize that the inserted α-helical form causes vesicle membrane disruption whereas the surface-bound ß form induces aggregation. © 1990, American Chemical Society. All rights reserved.