在人 A3 腺苷受体上设计、合成和结合同系物截断的 4'-硫代腺苷衍生物。
Design, synthesis, and binding of homologated truncated 4'-thioadenosine derivatives at the human A3 adenosine receptors.
机构信息
Department of Bioinspired Science, College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
出版信息
Bioorg Med Chem. 2010 Oct 1;18(19):7015-21. doi: 10.1016/j.bmc.2010.08.018. Epub 2010 Aug 14.
Abstract
We synthesized homologated truncated 4'-thioadenosine analogues 3 in which a methylene (CH(2)) group was inserted in place of the glycosidic bond of a potent and selective A(3) adenosine receptor antagonist 2. The analogues were designed to induce maximum binding interaction in the binding site of the A(3) adenosine receptor. However, all homologated nucleosides were devoid of binding affinity at all subtypes of adenosine receptors, indicating that free rotation through the single bond allowed the compound to adopt an indefinite number of conformations, disrupting the favorable binding interaction essential for receptor recognition.
摘要
我们合成了同源截断的 4′-硫代腺苷类似物 3，其中在强效和选择性 A(3) 腺苷受体拮抗剂 2 的糖苷键位置插入了一个亚甲基 (CH(2)) 基团。这些类似物的设计目的是在 A(3) 腺苷受体的结合部位诱导最大的结合相互作用。然而，所有同源化核苷都完全没有对所有亚型的腺苷受体的结合亲和力，这表明通过单键的自由旋转使化合物能够采用无数的构象，破坏了对受体识别至关重要的有利结合相互作用。
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