Photoreactive stapled BH3 peptides to dissect the BCL-2 family interactome.

Photoreactive stapled BH3 peptides to dissect the BCL-2 family interactome.
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DOI:
10.1016/j.chembiol.2010.09.015
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发表时间:
2010-12-22
影响因子:
--
通讯作者:
Walensky LD
Walensky LD
中科院分区:
生物1区
文献类型:
--
作者:
Braun CR;Mintseris J;Gavathiotis E;Bird GH;Gygi SP;Walensky LD

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定义蛋白质相互作用是发现生物途径、疾病机制和治疗干预机会的基础。为了利用结构多肽强大的结合亲和力和选择性来发现相互作用组,我们设计了光反应装订的BH3多肽螺旋,以共价捕获它们的生理bcl2家族靶标。交联型α-螺旋可以共价捕获静态和动态的蛋白质相互作用,并能够快速识别相互作用部位,在相互作用组发现和靶向药物设计之间提供了关键的联系。
Defining protein interactions forms the basis for discovery of biological pathways, disease mechanisms, and opportunities for therapeutic intervention. To harness the robust binding affinity and selectivity of structured peptides for interactome discovery, we engineered photoreactive stapled BH3 peptide helices that covalently capture their physiologic BCL-2 family targets. The crosslinking α-helices covalently trap both static and dynamic protein interactors, and enable rapid identification of interaction sites, providing a critical link between interactome discovery and targeted drug design.
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