Identification of chemical inhibitors of protein-kinase CK2 subunit interaction
Identification of chemical inhibitors of protein-kinase CK2 subunit interaction
复制标题
DOI：
10.1007/s11010-008-9821-6
复制
发表时间：
2008-09-01
影响因子：
4.3
通讯作者：
Cochet, Claude
中科院分区：
文献类型：
--
作者：
Laudet, Beatrice;Moucadel, Virginie;Cochet, Claude
蛋白激酶CK2是一个多亚基复合物，其动态组装是调控的关键点。干扰特定蛋白质-蛋白质相互作用的能力已经为影响细胞内选定蛋白质的功能提供了强有力的手段。CK2 β衍生的环肽靶向CK2 α上一个明确的疏水性口袋，以前被认为是CK2亚基组装[9]的有效抑制剂。作为合理设计低分子量CK2拮抗剂的第一步，我们在本研究中筛选了一系列鬼臼毒素吲哚类似物，以确定CK2亚基相互作用的化学抑制剂。我们报道了一种鬼臼毒素吲哚类似物的鉴定，作为一种化学配体，与CK2 α /CK2 β界面结合，诱导CK2 α /CK2 β组装的选择性破坏，并伴随CK2 α活性的抑制。
Protein kinase CK2 is a multi-subunit complex whose dynamic assembly appears as a crucial point of regulation. The ability to interfere with specific protein-protein interactions has already provided powerful means of influencing the functions of selected proteins within the cell. CK2 beta-derived cyclopeptides that target a well-defined hydrophobic pocket on CK2 alpha have been previously characterized as potent inhibitors of CK2 subunit assembly [9]. As a first step toward the rational design of low molecular weight CK2 antagonists, we have in the present study screened a collection of podophyllotoxine indolo-analogues to identify chemical inhibitors of the CK2 subunit interaction. We report the identification of a podophyllotoxine indolo-analogue as a chemical ligand that binds to the CK2 alpha/CK2 beta interface inducing selective disruption of the CK2 alpha/CK2 beta assembly and concomitant inhibition of CK2 alpha activity.