Targeted protein degradation: Emerging concepts and protein state-specific targeting principles.
Targeted protein degradation: Emerging concepts and protein state-specific targeting principles.
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DOI：
10.1016/j.cbpa.2021.102114
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发表时间：
2022-04
影响因子：
7.8
通讯作者：
中科院分区：
文献类型：
--
作者：
靶向蛋白降解物是一种异功能小分子，通过化学间隔物将靶配体或诱饵连接到e3连接酶粘合剂上。进入细胞后，这些配体触发靶蛋白、降解物和e3连接酶之间形成三元复合物，导致靶蛋白多泛素化和蛋白酶体降解。近年来，TPD作为一个领域迅速发展，成为药物发现和化学探针开发的首选方式。这是由这些分子独特的药理学驱动的，它允许快速和可逆地敲除目标蛋白。最近的研究表明，可以开发出对感兴趣的蛋白质的特定亚群具有特异性的降解物，从而产生了蛋白质状态特异性靶向的新兴概念。在这篇文章中，我们回顾了在基于它们的目标蛋白亚群之间区分的降解物的研究进展。激活状态、寡聚化状态、细胞定位状态和细胞类型。
Targeted protein degraders are heterobifunctional small molecules that link a target ligand or bait to an E3-ligase binder via a chemical spacer. Upon entering the cell, these ligands trigger the formation of a ternary complex between the target protein, degrader and E3-ligase, which leads to target polyubiquitination and proteasomal degradation. In recent years, TPD has expanded rapidly as a field, becoming the modality of choice in drug discovery and chemical probe development. This has been driven by the unique pharmacology of these molecules, which allows for fast and reversible knockdown of the target protein. Recent studies have demonstrated that degraders with specificity for a defined subpopulation of a protein-of-interest can be developed, giving rise to the emerging concept of protein state-specific targeting. In this article, we review advances towards developing degraders that differentiate between target protein subpopulations based on their; activation state, oligomerization state, cellular localization state, and cell type.
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影响因子：
16.6
作者：
Alabi S;Jaime-Figueroa S;Yao Z;Gao Y;Hines J;Samarasinghe KTG;Vogt L;Rosen N;Crews CM
通讯作者：
Crews CM
DOI：
10.1016/j.jbc.2021.100928
发表时间：
2021-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Pearce AC;Bamford MJ;Barber R;Bridges A;Convery MA;Demetriou C;Evans S;Gobbetti T;Hirst DJ;Holmes DS;Hutchinson JP;Jayne S;Lezina L;McCabe MT;Messenger C;Morley J;Musso MC;Scott-Stevens P;Manso AS;Schofield J;Slocombe T;Somers D;Walker AL;Wyce A;Zhang XP;Wagner SD
通讯作者：
Wagner SD
影响因子：
5.6
作者：
Silva MC;Haggarty SJ
通讯作者：
Haggarty SJ
影响因子：
14.8
作者：
Zhang, Xiaoyu;Crowley, Vincent M.;Cravatt, Benjamin F.
通讯作者：
Cravatt, Benjamin F.
影响因子：
64.8
作者：
Słabicki M;Yoon H;Koeppel J;Nitsch L;Roy Burman SS;Di Genua C;Donovan KA;Sperling AS;Hunkeler M;Tsai JM;Sharma R;Guirguis A;Zou C;Chudasama P;Gasser JA;Miller PG;Scholl C;Fröhling S;Nowak RP;Fischer ES;Ebert BL
通讯作者：
Ebert BL