Improved methods for targeting epigenetic reader domains of acetylated and methylated lysine.
Improved methods for targeting epigenetic reader domains of acetylated and methylated lysine.
复制标题
DOI：
10.1016/j.cbpa.2021.03.002
复制
发表时间：
2021-08
影响因子：
7.8
通讯作者：
Frye SV
中科院分区：
文献类型：
--
作者：
Engelberg IA;Foley CA;James LI;Frye SV
表观遗传阅读器蛋白负责解释组蛋白翻译后修饰(PTM)，已成为一系列疾病的新治疗靶点。化学探针在使靶标验证研究成为可能方面发挥了关键作用，并导致了癌症和炎症相关病理学的翻译进展。在这里，我们介绍了最近报道的识别酰化和甲基化赖氨酸的阅读器蛋白的探针。我们将讨论与实现读者结构域的有效拮抗相关的挑战，并回顾正在进行的克服这些障碍的努力，重点是靶向策略，包括模拟肽配体、变构调节剂和蛋白质降解剂的使用。
Responsible for interpreting histone post-translational modifications (PTMs), epigenetic reader proteins have emerged as novel therapeutic targets for a wide range of diseases. Chemical probes have been critical in enabling target validation studies and have led to translational advances in cancer and inflammation-related pathologies. Here, we present the most recently reported probes of reader proteins that recognize acylated and methylated lysine. We will discuss challenges associated with achieving potent antagonism of reader domains and review ongoing efforts to overcome these hurdles, focusing on targeting strategies including the use of peptidomimetic ligands, allosteric modulators, and protein degraders.
登录
查看更多内容
DOI：
10.1126/science.1249830
发表时间：
2014-10-31
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Baud MGJ;Lin-Shiao E;Cardote T;Tallant C;Pschibul A;Chan KH;Zengerle M;Garcia JR;Kwan TT;Ferguson FM;Ciulli A
通讯作者：
Ciulli A
影响因子：
7.3
作者：
Chan KH;Zengerle M;Testa A;Ciulli A
通讯作者：
Ciulli A
DOI：
10.1126/science.aaz8455
发表时间：
2020-04-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilan O;Rioja I;Knezevic K;Bell MJ;Yeung MM;Harker NR;Lam EYN;Chung CW;Bamborough P;Petretich M;Urh M;Atkinson SJ;Bassil AK;Roberts EJ;Vassiliadis D;Burr ML;Preston AGS;Wellaway C;Werner T;Gray JR;Michon AM;Gobbetti T;Kumar V;Soden PE;Haynes A;Vappiani J;Tough DF;Taylor S;Dawson SJ;Bantscheff M;Lindon M;Drewes G;Demont EH;Daniels DL;Grandi P;Prinjha RK;Dawson MA
通讯作者：
Dawson MA
选择性抑制BET溴结构域。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Erb MA;Scott TG;Li BE;Xie H;Paulk J;Seo HS;Souza A;Roberts JM;Dastjerdi S;Buckley DL;Sanjana NE;Shalem O;Nabet B;Zeid R;Offei-Addo NK;Dhe-Paganon S;Zhang F;Orkin SH;Winter GE;Bradner JE
通讯作者：
Bradner JE