首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Insights into binding modes of adenosine A(2B) antagonists with ligand-based and receptor-based methods.
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Insights into binding modes of adenosine A(2B) antagonists with ligand-based and receptor-based methods.

机译:用基于配体和基于受体的方法洞察腺苷A(2B)拮抗剂的结合模式。

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摘要

Ligand-based and receptor-based methods were used to investigate the binding modes of human adenosine A(2B) antagonists. At first, pharmacophore models were developed based on 140 diverse A(2B) antagonists from literature. Meanwhile, the structural model of A(2B) receptor was built up based on the crystal structure of human A(2A) receptor and validated by Induced Fit docking, Glide-XP and Glide-SP docking. Two models matched each other very well and some important implications were hence obtained. The residues of Phe173 and Glu174 in the second extracellular loop and Asn254 were crucial to the antagonists binding to form pi-pi stacking and hydrogen-bonding interactions. These findings would be very helpful for the discovery of novel and potent A(2B) antagonists.
机译:基于配体和受体的方法被用来研究人类腺苷A(2B)拮抗剂的结合模式。首先,基于来自文献的140种不同的A(2B)拮抗剂开发了药效团模型。同时,基于人A(2A)受体的晶体结构建立了A(2B)受体的结构模型,并通过诱导拟合对接,Glide-XP和Glide-SP对接进行了验证。两种模型彼此非常匹配,因此获得了一些重要含义。第二个细胞外环和Asn254中的Phe173和Glu174残基对于拮抗剂结合形成pi-pi堆积和氢键相互作用至关重要。这些发现对发现新型有效的A(2B)拮抗剂非常有帮助。

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