title: Membrane destabilizing activity of influenza virus hemagglutinin-based synthetic peptide: implications of critical glycine residue in fusion peptide.
abstract: Peptide III is a 20-residue synthetic model peptide based on the fusion peptide of influenza virus A/PR/8/34 strain and takes a secondary structure similar to the original peptide. While conserving the amphiphilic helical nature, 20 peptides to modify the bulkiness of side chains of peptide III were synthesized, and acid-induced membrane destabilization was assessed by aqueous content leakage from large unilamellar vesicles. Substitutions on the hydrophobic side decreased activity but showed less effect on the hydrophilic side, which confirmed the importance of the hydrophobic side for interaction with the membrane. Interestingly, substitution at the 13th Gly residue enhanced the amphiphilic helical nature but severely reduced activity. Correlation between alpha-helical content at acidic pH and the activity was not recognized, suggesting rather that the importance of this site was due to helix termination by glycine which allows N-terminal and C-terminal halves to behave as different secondary structural units.
authors.affiliation: Division of Molecular Biology and Information I, Kyoto University, Japan. matumoto@bms.Kuicr.Kyoto-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D008081:Liposomes; D008561:Membrane Fusion / Q000187:drug effects; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008081:Liposomes; D010446:Peptide Fragments; D014760:Viral Fusion Proteins