Hexapeptides that interfere with HIV-1 fusion peptide activity in liposomes block GP41-mediated membrane fusion.
Upon receptor-mediated activation, the gp41 hydrophobic, conserved fusion peptide inserts into the target membrane and promotes the kind of perturbations required for the progression of the HIV-cell fusion reaction. Using a synthetic combinatorial library we have identified all d-amino acid hexapeptide sequences that inhibited the fusion peptide capacity of perturbing model membranes. Two hexapeptides that effectively inhibited the fusion peptide in these systems were subsequently shown to inhibit cell-cell fusion promoted by gp41 expressed at cell surfaces. These observations might be of importance for understanding the mechanisms underlying fusion peptide activity and suggest new strategies for screening compounds that target these viral sequences.
Gómara
María J
MJ
Biofisika Unitatea, CSIC-UPV/EHU, and Biokimika Saila, Euskal Herriko Unibertsitatea, Posta Kutxa 644, 48080 Bilbao, Spain.
Lorizate
Maier
M
Huarte
Nerea
N
Mingarro
Ismael
I
Perez-Payá
Enrique
E
Nieva
José L
JL
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015700:HIV Envelope Protein gp41 / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism*; D008561:Membrane Fusion / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*
D015700:HIV Envelope Protein gp41; D008081:Liposomes; D010455:Peptides