Selective inhibition of MBNL1-CCUG interaction by small molecules toward potential therapeutic agents for myotonic dystrophy type 2 (DM2).
Selective inhibition of MBNL1-CCUG interaction by small molecules toward potential therapeutic agents for myotonic dystrophy type 2 (DM2).
复制标题
DOI：
10.1093/nar/gkr415
复制
发表时间：
2011-11-01
影响因子：
14.9
通讯作者：
Zimmerman SC
中科院分区：
文献类型：
--
作者：
Wong CH;Fu Y;Ramisetty SR;Baranger AM;Zimmerman SC
Myotonic dystrophy type 2 (DM2) is an incurable neuromuscular disease caused by expanded CCUG repeats that may exhibit toxicity by sequestering the splicing regulator MBNL1. A series of triaminotriazine- and triaminopyrimidine-based small molecules (ligands 1–3) were designed, synthesized and tested as inhibitors of the MBNL1–CCUG interaction. Despite the structural similarities of the triaminotriazine and triaminopyrimidine units, the triaminopyrimidine-based ligands bind with low micromolar affinity to CCUG repeats (Kd ∼ 0.1–3.6 µM) whereas the triaminotriazine ligands do not bind CCUG repeats. Importantly, these simple and small triaminopyrimidine ligands exhibit both strong inhibition (Ki ∼ 2 µM) of the MBNL1–CCUG interaction and high selectivity for CCUG repeats over other RNA targets. These experiments suggest these compounds are potential lead agents for the treatment of DM2.
登录
查看更多内容
影响因子：
4
作者：
Lee, Melissa M.;Pushechnikov, Alexei;Disney, Matthew D.
通讯作者：
Disney, Matthew D.
能够在体外抑制（CUG）重复RNA-MBNL1相互作用的分子的动态组合选择：发现靶向肌发育症的铅化合物（DM1）。
影响因子：
15
作者：
Gareiss, Peter C.;Sobczak, Krzysztof;McNaughton, Brian R.;Palde, Prakash B.;Thornton, Charles A.;Miller, Benjamin L.
通讯作者：
Miller, Benjamin L.
DOI：
10.1073/pnas.0903234106
发表时间：
2009-11-03
影响因子：
11.1
作者：
Warf, M. Bryan;Nakamori, Masayuki;Berglund, J. Andrew
通讯作者：
Berglund, J. Andrew
影响因子：
3.6
作者：
ROTH, B;STRELITZ, JZ
通讯作者：
STRELITZ, JZ
影响因子：
56.9
作者：
Liquori, CL;Ricker, K;Ranum, LPW
通讯作者：
Ranum, LPW