Binding inhibition of various influenza viruses by sialyllactose-modified trimer DNAs

• Published in: Bioorganic & medicinal chemistry letters Vol. 29; no. 5; pp. 744 - 748
• Main Authors: Yamabe, Miyuki, Kaihatsu, Kunihiro, Ebara, Yasuhito
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2019
• Subjects: Antiviral Agents - pharmacology; DNA - chemistry; DNA - pharmacology; DNA scaffold; Hemagglutinin; Humans; Influenza A virus - drug effects; Influenza A virus - metabolism; Influenza virus; Lactose - analogs & derivatives; Lactose - chemistry; Sialic acid; Sialic Acids - chemistry; Virus Attachment - drug effects; Sialic acid; DNA scaffold; Influenza virus; Hemagglutinin
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2018.12.064

[Display omitted] Sialyllactose (SL)-modified trimer DNAs with a similar SL presentation as their binding sites on influenza virus hemagglutinin (HA) trimer were designed and synthesized. These trimer DNAs showed high affinity for various influenza viruses, including A/Puerto Rico/08/34 (H1N1), A/Beijing/262/95 (H1N1), A/Yokohama/77/2008 (H1N1), and A/Panama/2007/99 (H3N2). Thus, presentation of SL residues on three vertexes of the scaffold as well as sialic acid binding sites on the HA trimer regardless of a tri-branched or triangular scaffold are important for high affinity for influenza viruses. These compounds have the potential for use in detection and as inhibitors of a broad spectrum of influenza viruses.