Exploring Rigid and Flexible Core Trivalent Sialosides for Influenza Virus Inhibition
| Autor: | Bettina G. Keller, Wolfgang Maison, Susanne Liese, Andreas Herrmann, Daniel Lauster, Natalija Peric, Pallavi Kiran, Stevan Aleksić, Sumati Bhatia, Carsten Fleck, Rainer Haag |
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| Rok vydání: | 2018 |
| Předmět: |
Tris
trivalent sialoside Molecular model Adamantane adamantane 010402 general chemistry Antiviral Agents Biochemistry 01 natural sciences Chemical synthesis Catalysis Virus Structure-Activity Relationship chemistry.chemical_compound 500 Natural sciences and mathematics::530 Physics::530 Physics Influenza Human Humans viruses ddc:530 influenza inhibitors influenza inhibitor Full Paper 010405 organic chemistry Organic Chemistry General Chemistry Full Papers Combinatorial chemistry 0104 chemical sciences oligoethylene glycol chemistry Influenza A virus adamantane core Sialic Acids Protein Binding |
| Zdroj: | Chemistry-A European Journal Chemistry (Weinheim an Der Bergstrasse, Germany) |
| ISSN: | 1521-3765 0947-6539 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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