Novel trivalent anti-influenza reagent

作者：Feng Fei; Miura Nobuaki; Isoda Norikazu; Sakoda Yoshihiro; Okamatsu Masatoshi; Kida Hiroshi^*; Nishimura Shin Ichiro

来源：Bioorganic & Medicinal Chemistry Letters, 2010, 20(12): 3772-3776.

DOI：10.1016/j.bmcl.2010.04.060

• Computer-based drug design
• Anti-influenza virus infection
• Trivalent glycoside
• Scaffold

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 Neu5A alpha 2,3Gal beta 1,4Glc 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 mu M at 4 degrees C.

• 出版日期2010-6-15