tetano
Editor, Senior Moderator
Bioorg Med Chem Lett. 2010 Apr 18. [Epub ahead of print]
Novel trivalent anti-influenza reagent.
Feng F, Miura N, Isoda N, Sakoda Y, Okamatsu M, Kida H, Nishimura SI.
Department of Advanced Transdisciplinary Science, Faculty of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
Abstract
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 400muM at 4 degrees C. Copyright ? 2010 Elsevier Ltd. All rights reserved.
PMID: 20488701 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20488701
Novel trivalent anti-influenza reagent.
Feng F, Miura N, Isoda N, Sakoda Y, Okamatsu M, Kida H, Nishimura SI.
Department of Advanced Transdisciplinary Science, Faculty of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
Abstract
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 400muM at 4 degrees C. Copyright ? 2010 Elsevier Ltd. All rights reserved.
PMID: 20488701 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20488701