Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited
Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited
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DOI：
10.1021/acsmedchemlett.6b00311
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发表时间：
2017-02-01
影响因子：
4.2
通讯作者：
Kolocouris, Antonios
中科院分区：
文献类型：
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作者：
Drakopoulos, Antonios;Tzitzoglaki, Christina;Kolocouris, Antonios
固态NMR（ssNMR）研究的最新发现表明金刚乙胺的（R）-对映体与完整M2蛋白的结合亲和力高于（S）-对映体。这些发现引起了我们的兴趣，我们应用功能测定，如抗病毒测定和电生理学（EP），来评估金刚乙胺对映体与M2蛋白通道的结合亲和力。出乎意料的是，在两种对映异构体之间没有发现显著差异。我们基于M2蛋白功能的实验数据得到了炼金术自由能的进一步支持。计算和等温滴定量热法（ITC），允许评价金刚乙胺对映体与M2 TM孔的结合亲和力。两种对映体具有相似的通道阻断、亲和力和抗病毒效力。
Recent findings from solid state NMR (ssNMR) studies suggested that the (R)-enantiomer of rimantadine binds to the full M2 protein with higher affinity than the (S)-enantiomer. Intrigued by these findings, we applied functional assays, such as antiviral assay and electrophysiology (EP), to evaluate the binding affinity of rimantadine enantiomers to the M2 protein channel. Unexpectedly, no significant difference was found between the two enantiomers. Our experimental data based on the full M2 protein function were further supported by alchemical free energy. calculations and isothermal titration calorimetry (ITC) allowing an evaluation of the binding affinity of rimantadine enantiomers to the M2TM pore. Both enantiomers have similar channel blockage, affinity, and antiviral potency.