Understanding the Boron鈥揘itrogen Interaction and Its Possible Implications in Drug Design

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• 作者：Hao Dong ; Wei Li ; Jianwei Sun ; Shuhua Li ; Michael L. Klein
• 刊名：Journal of Physical Chemistry B
• 出版年：2015
• 出版时间：November 12, 2015
• 年：2015
• 卷：119
• 期：45
• 页码：14393-14401
• 全文大小：522K
• ISSN：1520-5207

文摘

2-Aminoethoxydiphenylborate (2-APB) is a broad-spectrum modulator of various membrane proteins. Specifically, it exhibits concentration dependent modulation of calcium signaling through store-operated calcium (SOC) channels: low micromolar concentration of 2-APB stimulates SOC entry while a higher concentration induces complete inhibition. Ab initio quantum chemical calculations show that the relative stability of the two major isomers of 2-APB (cyclic and extended) is about 8 kcal/mol. The dual functionality of 2-APB for SOC channels is thus likely associated with its ability to switch among isomeric forms, suited to different binding sites in the SOC channels with distinct binding affinities. Importantly, the moderate relative stability of different isomers results from a delicate balance between the intramolecular boron鈥搉itrogen coordinate bond with strength about 鈭?5 kcal/mol and ring strain engendered by cyclic oligomerization. The synergistic effect of these two factors likely makes 2-APB an ideal dual effect drug.