Novel trivalent anti-influenza reagent.
We designed and synthesized novel trivalent anti-influenza reagents. Sialyllactose was located at the terminal of each valence which aimed to block each receptor-binding site of the hemagglutinin (HA) trimer on the surface of the virus. Structural analyses were carried out with a model which was constructed with a computer simulation. A previously reported cyclic glycopeptide blocker [Ohta, T.; Miura, N.; Fujitani, N.; Nakajima, F.; Niikura, K.; Sadamoto, R.; Guo, C.-T.; Suzuki, T.; Suzuki, Y.; Monde, K.; Nishimura, S.-I. Angew. Chem. Int. Ed., 2003, 42, 5186] bound to the HA in the model. The analyses suggest that the glutamine residue in the cyclic peptide bearing Neu5Acalpha2,3Galbeta1,4Glc trisaccharide via a linker interacts with the Gln189 in HA through hydrogen bonding. The present anti-influenza reagents likely interact with a glutamine residue included in the vicinity of Gln189. A plague reduction assay of the influenza virus, A/PR/8/1934 (H1N1), was performed in MDCK cells to evaluate for the synthesized compounds to inhibit viral replication. One of the compounds showed approximately 85% inhibition at the concentration of 400 microM at 4 degrees C.
Feng
Fei
F
Department of Advanced Transdisciplinary Science, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
Miura
Nobuaki
N
Isoda
Norikazu
N
Sakoda
Yoshihiro
Y
Okamatsu
Masatoshi
M
Kida
Hiroshi
H
Nishimura
Shin-Ichiro
S
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D004285:Dogs; D015195:Drug Design; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000187:drug effects*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D007251:Influenza, Human / Q000188:drug therapy; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D011991:Receptors, Virus; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D010456:Peptides, Cyclic; D011991:Receptors, Virus