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Experimental Characterization of the Binding Affinities between Proapoptotic BH3 Peptides and Antiapoptotic Bcl‐2 Proteins
ChemMedChem ( IF 3.6 ) Pub Date : 2018-08-07 , DOI: 10.1002/cmdc.201800321 Wenna Kong 1, 2 , Mi Zhou 2 , Qing Li 2 , Wenjie Fan 2 , Haixia Lin 1 , Renxiao Wang 2
ChemMedChem ( IF 3.6 ) Pub Date : 2018-08-07 , DOI: 10.1002/cmdc.201800321 Wenna Kong 1, 2 , Mi Zhou 2 , Qing Li 2 , Wenjie Fan 2 , Haixia Lin 1 , Renxiao Wang 2
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The Bcl‐2 family proteins are key regulators of the intrinsic apoptotic pathway and are among the validated targets for developing anticancer drugs. Protein–protein interactions between the pro‐ and antiapoptotic members of this family determine mitochondrial outer‐membrane permeabilization. Elucidating such protein–protein interactions in a quantitative way is helpful for network pharmacology studies on the Bcl‐2 family, which, in turn, will provide valuable guidance for developing new anticancer therapies. In this study, the binding affinities of the BH3 peptides derived from eight proapoptotic BH3‐only proteins (i.e., Bid, Bim, Puma, Noxa, Bad, Bmf, Bik, Hrk) against five well‐studied antiapoptotic proteins (i.e., Bcl‐xL, Bcl‐2, Mcl‐1, Bcl‐w, Bfl‐1) in the Bcl‐2 family have been measured. Three different types of binding assay (i.e., surface plasmon resonance, fluorescence polarization, and homogeneous time‐resolved fluorescence) were employed for cross‐validation. The results confirmed that each proapoptotic BH3 peptide exhibited a distinct binding profile against the five antiapoptotic proteins. The binding data obtained herein serve as a fresh update or correction to existing knowledge. It is expected that such binding data will be helpful for building more accurate mathematical network models for depicting the complex protein–protein interactions within the Bcl‐2 family.
中文翻译：
实验性表征促凋亡BH3肽与抗凋亡Bcl-2蛋白之间的结合亲和力
Bcl-2家族蛋白是内在凋亡途径的关键调节剂，并且是开发抗癌药物的有效靶标之一。该家族的抗凋亡成员之间的蛋白相互作用决定了线粒体的外膜通透性。定量阐明这种蛋白质之间的相互作用对Bcl-2家族的网络药理学研究是有帮助的，而Bcl-2家族又将为开发新的抗癌疗法提供有价值的指导。在这项研究中，源自八个促凋亡的仅BH3蛋白（即Bid，Bim，Puma，Noxa，Bad，Bmf，Bik，Hrk）的BH3肽与五个经过充分研究的抗凋亡蛋白（即Bcl- X大号，Bcl-2系列中的Bcl-2，Mcl-1，Bcl-w，Bfl-1）。交叉验证使用了三种不同类型的结合测定（即，表面等离子体共振，荧光偏振和均相时间分辨荧光）。结果证实了每个促凋亡的BH3肽对五个抗凋亡蛋白均表现出独特的结合特性。本文获得的绑定数据用作对现有知识的最新更新或更正。预计这种结合数据将有助于建立更精确的数学网络模型，以描述Bcl-2家族内复杂的蛋白质相互作用。
更新日期：2018-08-07
中文翻译：
实验性表征促凋亡BH3肽与抗凋亡Bcl-2蛋白之间的结合亲和力
Bcl-2家族蛋白是内在凋亡途径的关键调节剂，并且是开发抗癌药物的有效靶标之一。该家族的抗凋亡成员之间的蛋白相互作用决定了线粒体的外膜通透性。定量阐明这种蛋白质之间的相互作用对Bcl-2家族的网络药理学研究是有帮助的，而Bcl-2家族又将为开发新的抗癌疗法提供有价值的指导。在这项研究中，源自八个促凋亡的仅BH3蛋白（即Bid，Bim，Puma，Noxa，Bad，Bmf，Bik，Hrk）的BH3肽与五个经过充分研究的抗凋亡蛋白（即Bcl- X大号，Bcl-2系列中的Bcl-2，Mcl-1，Bcl-w，Bfl-1）。交叉验证使用了三种不同类型的结合测定（即，表面等离子体共振，荧光偏振和均相时间分辨荧光）。结果证实了每个促凋亡的BH3肽对五个抗凋亡蛋白均表现出独特的结合特性。本文获得的绑定数据用作对现有知识的最新更新或更正。预计这种结合数据将有助于建立更精确的数学网络模型，以描述Bcl-2家族内复杂的蛋白质相互作用。
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