首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >A structure-activity relationship study on position-2 of the Galpha(s) C-terminal peptide able to inhibit G(s) activation by A(2A) adenosine receptor.
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A structure-activity relationship study on position-2 of the Galpha(s) C-terminal peptide able to inhibit G(s) activation by A(2A) adenosine receptor.

机译:结构活性关系研究的Galpha C末端肽的位置2能够抑制A(2A)腺苷受体激活G(s)。

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摘要

For some years synthetic peptides corresponding to the C-terminal sequence of Galpha proteins represented an useful tool to study the molecular mechanism of the interaction between these proteins and the G protein coupled receptors. Recently, we have focused our attention on the study of the A(2A) receptor-G(s) protein system. We have synthesised a series of 11-mer peptides from the Galpha(s) C-terminus in which residue at position-2 (Leu(393)) has been alternatively substituted with amino acids having different physico-chemical properties. The aim of our work was to probe the role played by Leu(393) in the receptor/Galpha(s) interaction. All synthetic peptides were tested for their ability to affect the adenylyl cyclase activity stimulated by agonist activation of A(2A) adenosine receptors. Our data point out a relevant role played by the side chain of this residue for a correct G protein/receptor coupling, even though the presence of other residues at position-2 of Galpha(s) C-terminus is tolerated. Furthermore, molecular dynamics calculations on the peptides having greater activity show a correlation between the spatial arrangement of the side chain of residue at position-2 and biological activity of synthetic peptides.
机译:多年来,对应于Galpha蛋白C端序列的合成肽代表了研究这些蛋白与G蛋白偶联受体之间相互作用的分子机制的有用工具。最近,我们将注意力集中在A(2A)受体G(s)蛋白质系统的研究上。我们已经从Galpha(s)C端合成了一系列11-mer肽,其中2位(Leu(393))处的残基已被具有不同理化性质的氨基酸替代。我们工作的目的是探究Leu(393)在受体/ Galpha相互作用中的作用。测试所有合成肽的能力,以影响由A(2A)腺苷受体激动剂激活而刺激的腺苷酸环化酶活性。我们的数据指出该残基的侧链对于正确的G蛋白/受体偶联起着相关的作用,即使可以容忍Galpha(s)C端的2位存在其他残基。此外,对具有更高活性的肽进行的分子动力学计算表明,位置2处残基侧链的空间排列与合成肽的生物学活性之间存在相关性。

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