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Bilayer stabilizing peptides and the inhibition of viral infection: antimeasles activity of carbobenzoxy-Ser-Leu-amide
Authors:Richard M Epand  Thomas J Lobl  H E Renis
Institution:(1) Department of Biochemistry, McMaster University Health Science Centre, L8N 3Z5 Hamilton, Ontario, Canada;(2) Biopolymer Chemistry, The Upjohn Company, 49001 Kalamazoo, MI, USA;(3) Cancer and Viral Disease Research, The Upjohn Company, 49001 Kalamazoo, MI, USA
Abstract:A number of carbobenzoxy-dipeptide-amides raise the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine (stabilizes the bilayer). The potency of the peptides in stabilizing the bilayer phase is Z-Tyr-Leu-NH2= Z-Gly-Phe-NH2>Z-Ser-Leu-NH2>Z-Gly-Leu-NH2>Z-Gly-Gly-NH2. A linear correlation was found between the respective HPLC retention time parameterkprime for the peptide and the slope of the bilayer stabilization curve determined with model membranes by differential scanning calorimetry. One dipeptide, Z-Ser-Leu-NH2, reduces measles virus cytopathic effect (CPE) in Vero cells. The mechanism by which this peptide reduces the CPE is not known, although some peptides which raise the bilayer to hexagonal phase transition temperature of phospholipids inhibit membrane fusion.Abbreviations Z carbobenzoxy - DEPE dielaidoylphosphatidylethanolamine - DSC differential scanning calorimetry - HPLC high pressure liquid chromatography - CPE cytopathic effect To whom correspondence should be addressed.
Keywords:virus inhibitors  measles virus  peptide synthesis  membrane fusion  membrane stabilization  hexagonal phase
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