tetano
Editor, Senior Moderator
Bioorg Med Chem. 2016 Jan 21. pii: S0968-0896(16)30039-6. doi: 10.1016/j.bmc.2016.01.039. [Epub ahead of print]
[h=1]Heptapeptide ligands against receptor-binding sites of influenza hemagglutinin toward anti-influenza therapy.[/h] Matsubara T[SUP]1[/SUP], Onishi A[SUP]1[/SUP], Yamaguchi D[SUP]1[/SUP], Sato T[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The initial attachment of influenza virus to cells is the binding of hemagglutinin (HA) to the sialyloligosaccharide receptor; therefore, the small molecules that inhibit the sugar-protein interaction are promising as HA inhibitors to prevent the infection. We herein demonstrate that sialic acid-mimic heptapeptides are identified through a selection from a primary library against influenza virus HA. In order to obtain lead peptides, an affinity selection from a phage-displayed random heptapeptide library was performed with the HAs of the H1 and H3 strains, and two kinds of the HA-binding peptides were identified. The binding of the peptides to HAs was inhibited in the presence of sialic acid, and plaque assays indicated that the corresponding N-stearoyl peptide strongly inhibited infections by the A/Aichi/2/68 (H3N2) strain of the virus. Alanine scanning of the peptides indicated that arginine and proline were responsible for binding. The affinities of several mutant peptides with single-amino-acid substitutions against H3 HA were determined, and corresponding docking studies were performed. A Spearman analysis revealed a correlation between the affinity of the peptides and the docking study. These results provide a practicable method to design of peptide-based HA inhibitors that are promising as anti-influenza drugs.
Copyright ? 2016 Elsevier Ltd. All rights reserved.
[h=4]KEYWORDS:[/h] Hemagglutinin; Heptapeptide library; Peptide drug; Phage display; Sialic acid-mimic
PMID: 26833245 [PubMed - as supplied by publisher]
[h=1]Heptapeptide ligands against receptor-binding sites of influenza hemagglutinin toward anti-influenza therapy.[/h] Matsubara T[SUP]1[/SUP], Onishi A[SUP]1[/SUP], Yamaguchi D[SUP]1[/SUP], Sato T[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The initial attachment of influenza virus to cells is the binding of hemagglutinin (HA) to the sialyloligosaccharide receptor; therefore, the small molecules that inhibit the sugar-protein interaction are promising as HA inhibitors to prevent the infection. We herein demonstrate that sialic acid-mimic heptapeptides are identified through a selection from a primary library against influenza virus HA. In order to obtain lead peptides, an affinity selection from a phage-displayed random heptapeptide library was performed with the HAs of the H1 and H3 strains, and two kinds of the HA-binding peptides were identified. The binding of the peptides to HAs was inhibited in the presence of sialic acid, and plaque assays indicated that the corresponding N-stearoyl peptide strongly inhibited infections by the A/Aichi/2/68 (H3N2) strain of the virus. Alanine scanning of the peptides indicated that arginine and proline were responsible for binding. The affinities of several mutant peptides with single-amino-acid substitutions against H3 HA were determined, and corresponding docking studies were performed. A Spearman analysis revealed a correlation between the affinity of the peptides and the docking study. These results provide a practicable method to design of peptide-based HA inhibitors that are promising as anti-influenza drugs.
Copyright ? 2016 Elsevier Ltd. All rights reserved.
[h=4]KEYWORDS:[/h] Hemagglutinin; Heptapeptide library; Peptide drug; Phage display; Sialic acid-mimic
PMID: 26833245 [PubMed - as supplied by publisher]