Discovery of a fluorescent probe with HDAC6 selective inhibition.
Discovery of a fluorescent probe with HDAC6 selective inhibition.
复制标题
DOI：
10.1016/j.ejmech.2017.10.022
复制
发表时间：
2017-12-01
影响因子：
6.7
通讯作者：
Yao TP
中科院分区：
文献类型：
--
作者：
Zhang Y;Yan J;Yao TP
There is increasing interest in discovering HDAC6 selective inhibitors as chemical probes to elucidate the biological functions of HDAC6 and ultimately as new therapeutic agents. Small-molecular fluorescent probes are widely used to detect target protein location and function, identify protein complex composition in biological processes of interest. In the present study, structural modification of the previously reported compound 4MS leads to two novel fluorescent HDAC inhibitors, 6a and 6b. Determination of IC50 values against the panel of Zn2+ dependent HDACs (HDAC1-11) reveals that 6b is a HDAC6 selective inhibitor, which can induce hyperacetylation of tubulin but not histone H4. Importantly, fluorescent and immunofluorescent analyses of cells treated with the proteasome inhibitor MG132 demonstrates that 6b can selectively target and image HDAC6 within the inclusion body, the aggresome. These results identify 6b not only as a HDAC6 selective inhibitor but also as a fluorescent probe for imaging HDAC6 and investigating the roles of HDAC6 in various physiological and pathological contexts.
登录
查看更多内容
影响因子：
64.8
作者：
Hubbert, C;Guardiola, A;Yao, TP
通讯作者：
Yao, TP
影响因子：
64.5
作者：
Kawaguchi, Y;Kovacs, JJ;Yao, TP
通讯作者：
Yao, TP
影响因子：
4.7
作者：
Ding H;Dolan PJ;Johnson GV
通讯作者：
Johnson GV
DOI：
10.1097/ta.0000000000000510
发表时间：
2015-02
期刊：
The journal of trauma and acute care surgery
影响因子：
--
作者：
Li Y;Zhao T;Liu B;Halaweish I;Mazitschek R;Duan X;Alam HB
通讯作者：
Alam HB
DOI：
10.1083/jcb.143.7.1883
发表时间：
1998-12-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Johnston JA;Ward CL;Kopito RR
通讯作者：
Kopito RR