DESIGN OF A SHORT MEMBRANE-DESTABILIZING PEPTIDE COVALENTLY BOUND TO LIPOSOMES

We characterized the physical and biological properties of a 14-residu e amphipathic sequence called SFP (for short fusogenic peptide). At ac idic pH, this short synthetic peptide interacts with various phospholi pidic monolayers. These interactions were correlated with a pH-depende nt conformational transition of SFP resulting in a hydrophobic alpha-h elical structure. The hemolysis assay showed a pH-dependent weak membr ane destabilizing activity of SFP. However, membrane anchoring of SFP through a covalently bound myristic acid enhanced by 1000-fold its mem brane-destabilizing power. Moreover, SFP covalently bound to fluoresce nt-labeled liposomes induced a pH-dependent mixing of both membranes. SFP, a small synthetic peptide, is thus able to mimick many aspects of viral protein-induced membrane fusion: conformational change, membran e destabilization, membrane anchoring and finally pH-dependent lipid m ixing.