tetano
Editor, Senior Moderator
Chemistry. 2018 Oct 8. doi: 10.1002/chem.201804826. [Epub ahead of print]
[h=1]Exploring rigid and flexible core trivalent sialosides for influenza virus inhibition.[/h] Haag R[SUP]1[/SUP], Kiran P[SUP]2[/SUP], Bhatia S[SUP]3[/SUP], Lauster D[SUP]4[/SUP], Aleksić S[SUP]5[/SUP], Fleck C[SUP]6[/SUP], Peric N[SUP]6[/SUP], Maison W[SUP]6[/SUP], Liese S[SUP]7[/SUP], Keller BG[SUP]5[/SUP], Herrmann A[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] trivalent sialoside, adamantane core, influenza inhibitor, oligoethylene glycol
PMID: 30295350 DOI: 10.1002/chem.201804826
[h=1]Exploring rigid and flexible core trivalent sialosides for influenza virus inhibition.[/h] Haag R[SUP]1[/SUP], Kiran P[SUP]2[/SUP], Bhatia S[SUP]3[/SUP], Lauster D[SUP]4[/SUP], Aleksić S[SUP]5[/SUP], Fleck C[SUP]6[/SUP], Peric N[SUP]6[/SUP], Maison W[SUP]6[/SUP], Liese S[SUP]7[/SUP], Keller BG[SUP]5[/SUP], Herrmann A[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] trivalent sialoside, adamantane core, influenza inhibitor, oligoethylene glycol
PMID: 30295350 DOI: 10.1002/chem.201804826