tetano
Editor, Senior Moderator
Antivir Chem Chemother. 2012 Feb 20. doi: 10.3851/IMP2553. [Epub ahead of print]
Novel thiosialosides tethered to metal nanoparticles as potent influenza A virus hemagglutinin blockers.
Feng F, Sakoda Y, Ohyanagi T, Nagahori N, Shibuya H, Okamastu M, Miura N, Kida H, Nishimura SI.
Source
Division of Drug Discovery Research, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
Abstract
BACKGROUND:
The purpose of this study is to develop a new class of influenza A virus hemagglutinin (HA) blockers by tethering thiosialoside molecules to metal nanoparticles and producing glycoclusters that enhance the affinity of HA binding by N-acetylneuraminic acid.
METHODS:
Oxygen of the glycoside bond of sialoside was replaced with sulfur to prevent hydrolytic digestion of the N-acetylneuraminic acid residue by viral neuraminidase. Two novel thiosialosides, α-2-S-[p-(N-levulinyl)aminophenyl]-5-N-acetylneuraminic acid [Neu5Ac-S-Lev (1)] and α-2-S-[m-(N-levulinyl)aminobenzyl]-5-N-acetylneuraminic acid [Neu5Ac-S-CH(2)-Lev (2)], were tethered onto the surface of metal nanoparticles via an aminooxy functionalized thiol linker (aoSH) in a glycoblotting reaction. Gold and silver nanoparticles were coated simultaneously with 11-mercaptoundecyl phosphorylcholine (PCSH) to reduce nonspecific adsorption of proteins. Phosphorylcholine self-assembled monolayer coated metals displaying clustered Neu5Ac (Neu5Ac-PCSAM-Au and Neu5Ac-PCSAM-Ag) were subjected to hemagglutination-inhibition (HI) assays using the influenza A virus strain A/PR/8/1934 (H1N1).
RESULTS:
Glyconanoparticles with thiosialosides had potent HI activities. In particular, Neu5Ac-PCSAM-Au with 9.8-?M Neu5Ac and a diameter of 20 nm was the most potent HA inhibitor. The versatility of this strategy was demonstrated by similar submicromolar HI activities of Neu5Ac-PCSAM-Ag with diameters of 50 nm and 150 nm.
CONCLUSIONS:
Glycosylated metal nanoparticles were designed and synthesized as potent influenza A virus HA blockers. This study may contribute to the acceleration of the discovery of a new class of nanoparticle anti-influenza drugs.
PMID:
23425865
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23425865
Novel thiosialosides tethered to metal nanoparticles as potent influenza A virus hemagglutinin blockers.
Feng F, Sakoda Y, Ohyanagi T, Nagahori N, Shibuya H, Okamastu M, Miura N, Kida H, Nishimura SI.
Source
Division of Drug Discovery Research, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
Abstract
BACKGROUND:
The purpose of this study is to develop a new class of influenza A virus hemagglutinin (HA) blockers by tethering thiosialoside molecules to metal nanoparticles and producing glycoclusters that enhance the affinity of HA binding by N-acetylneuraminic acid.
METHODS:
Oxygen of the glycoside bond of sialoside was replaced with sulfur to prevent hydrolytic digestion of the N-acetylneuraminic acid residue by viral neuraminidase. Two novel thiosialosides, α-2-S-[p-(N-levulinyl)aminophenyl]-5-N-acetylneuraminic acid [Neu5Ac-S-Lev (1)] and α-2-S-[m-(N-levulinyl)aminobenzyl]-5-N-acetylneuraminic acid [Neu5Ac-S-CH(2)-Lev (2)], were tethered onto the surface of metal nanoparticles via an aminooxy functionalized thiol linker (aoSH) in a glycoblotting reaction. Gold and silver nanoparticles were coated simultaneously with 11-mercaptoundecyl phosphorylcholine (PCSH) to reduce nonspecific adsorption of proteins. Phosphorylcholine self-assembled monolayer coated metals displaying clustered Neu5Ac (Neu5Ac-PCSAM-Au and Neu5Ac-PCSAM-Ag) were subjected to hemagglutination-inhibition (HI) assays using the influenza A virus strain A/PR/8/1934 (H1N1).
RESULTS:
Glyconanoparticles with thiosialosides had potent HI activities. In particular, Neu5Ac-PCSAM-Au with 9.8-?M Neu5Ac and a diameter of 20 nm was the most potent HA inhibitor. The versatility of this strategy was demonstrated by similar submicromolar HI activities of Neu5Ac-PCSAM-Ag with diameters of 50 nm and 150 nm.
CONCLUSIONS:
Glycosylated metal nanoparticles were designed and synthesized as potent influenza A virus HA blockers. This study may contribute to the acceleration of the discovery of a new class of nanoparticle anti-influenza drugs.
PMID:
23425865
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23425865