Exploring Rigid and Flexible Core Trivalent Sialosides for Influenza Virus Inhibition,Chemistry - A European Journal

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Exploring Rigid and Flexible Core Trivalent Sialosides for Influenza Virus Inhibition
Chemistry - A European Journal ( IF 3.9 ) Pub Date : 2018-11-22 , DOI: 10.1002/chem.201804826
Pallavi Kiran ₁ , Sumati Bhatia ₁ , Daniel Lauster ₂ , Stevan Aleksić ₃ , Carsten Fleck ₄ , Natalija Peric ₄ , Wolfgang Maison ₄ , Susanne Liese _{5,

6} , Bettina G. Keller ₃ , Andreas Herrmann ₂ , Rainer Haag ₁

Affiliation

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.

中文翻译：

探索刚性和灵活的核心三价唾液中抑制流感病毒的能力

在本文中，描述了带有可与A型流感病毒（IAV）X31的突突蛋白相互作用的寡乙二醇（OEG）间隔基的可官能化的刚性和柔性核心三价唾液酸的化学合成和结合分析。尽管基于Tris的柔性三价sialosides具有微摩尔结合常数，但基于刚性金刚烷核的三价粘合剂以三摩尔结合常数和血凝抑制常数为主导的柔性三脚架化合物。模拟研究表明，长OEG间隔基的构象罚分增加。使用分子建模和模拟以及生物物理分析的系统方法，这些发现强调了支架刚度的重要性以及与间隔物长度优化相关的挑战。

更新日期：2018-11-22

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