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Exploring rigid and flexible core trivalent sialosides for influenza virus inhibition

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  • Exploring rigid and flexible core trivalent sialosides for influenza virus inhibition

    Chemistry. 2018 Oct 8. doi: 10.1002/chem.201804826. [Epub ahead of print]
    Exploring rigid and flexible core trivalent sialosides for influenza virus inhibition.

    Haag R1, Kiran P2, Bhatia S3, Lauster D4, Aleksić S5, Fleck C6, Peric N6, Maison W6, Liese S7, Keller BG5, Herrmann A4.
    Author information

    Abstract

    We describe the chemical synthesis and binding analysis of functionalizable rigid and flexible core trivalent sialosides bearing oligoethylene glycol (OEG) spacers interacting with spike proteins of influenza A virus (IAV) X31. Although the flexible tris-based trivalent sialosides achieved micromolar binding constants, a trivalent binder based on a rigid adamantane core dominated flexible tripodal compounds with micromolar binding and hemagglutination inhibition constants. Simulation studies indicated increased conformational penalties for long OEG spacers. Using a systematic approach with molecular modeling and simulations as well as biophysical analysis, our findings emphasize on the importance of the scaffold rigidity and the challenges associated with the spacer length optimization.


    KEYWORDS:

    trivalent sialoside, adamantane core, influenza inhibitor, oligoethylene glycol

    PMID: 30295350 DOI: 10.1002/chem.201804826
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