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Exploring Rigid and Flexible Core Trivalent Sialosides for Influenza Virus Inhibition
Author(s) -
Kiran Pallavi,
Bhatia Sumati,
Lauster Daniel,
Aleksić Stevan,
Fleck Carsten,
Peric Natalija,
Maison Wolfgang,
Liese Susanne,
Keller Bettina G.,
Herrmann Andreas,
Haag Rainer
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201804826
Subject(s) - chemistry , adamantane , molecular model , stereochemistry , combinatorial chemistry , biophysics , organic chemistry , biology
Herein, 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 is described. 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, these findings emphasize on the importance of the scaffold rigidity and the challenges associated with the spacer length optimization.