Identification of a benzo imidazole thiazole derivative as the specific irreversible inhibitor of protein tyrosine phosphatase.
Identification of a benzo imidazole thiazole derivative as the specific irreversible inhibitor of protein tyrosine phosphatase.
复制标题
鉴定苯并咪唑噻唑衍生物作为蛋白酪氨酸磷酸酶的特异性不可逆抑制剂。
DOI：
10.1016/j.bmcl.2016.08.024
复制
发表时间：
2016-10
影响因子：
2.7
通讯作者：
Sun Jin-Peng
中科院分区：
文献类型：
--
作者：
Ge Lin;Li Kang-Shuai;Li Meng-Meng;Xiao Peng;Hou Xu-Ben;Chen Xu;Liu Hong-da;Lin Amy;Yu Xiao;Ren Gui-Jie;Fang Hao;Sun Jin-Peng
蛋白酪氨酸磷酸酶（Protein tyrosine phosphatases，PTPs）在细胞增殖、分化、免疫应答和神经活动等生理过程中发挥着重要作用。PTP活性的不适当调节可能导致人类疾病，如癌症或糖尿病。PTP的功能研究可以大大促进化学探针，共价标记的活性位点的PTP通过活性依赖的化学反应。在这里，我们将化合物E4表征为一类新的PTP活性探针。化合物E4以时间和浓度依赖性方式抑制STEP。进一步的研究表明，化合物E4以时间依赖性方式抑制一系列PTP，而它对金属依赖性蛋白磷酸酶几乎没有抑制作用。总之，这种新鉴定的PTP共价抑制剂有可能被开发为活性位点Cys导向的PTP探针，以研究PTP在细胞信号传导中的活性特性。
Protein tyrosine phosphatases (PTPs) play key roles in many physiological processes, including cell proliferation, differentiation, immune responses and neural activities. Inappropriate regulation of the PTP activity could lead to human diseases, such as cancer or diabetes. Functional studies of PTP can be greatly facilitated by chemical probes that covalently label the active site of a PTP through an activity-dependent chemical reaction. Here, we characterize compoundE4as a new class of PTP activity probes. CompoundE4inactivate STEP in a time- and concentration-dependent fashion. Further study showed that compoundE4inhibits a series of PTPs in a time dependent manner, whereas it shows little or no inhibition toward metal dependent protein phosphatases. Collectively, this new identified covalent inhibitor of PTPs has the potential to be developed to an active site Cys directed PTP probes to study the active properties of the PTPs in cell signaling.
登录
查看更多内容
影响因子：
15
作者：
Zhang, Sheng;Liu, Sijiu;Tao, Rongya;Wei, Dan;Chen, Lan;Shen, Weihua;Yu, Zhi-Hong;Wang, Lina;Jones, David R.;Dong, Xiaocheng C.;Zhang, Zhong-Yin
通讯作者：
Zhang, Zhong-Yin
影响因子：
16.8
作者：
Wiesmann, C;Barr, KJ;Hansen, SK
通讯作者：
Hansen, SK
影响因子：
5.8
作者：
Velaga, MR;Wilson, V;Pearce, SHS
通讯作者：
Pearce, SHS
影响因子：
4.6
作者：
Rook GA;Raison CL;Lowry CA
通讯作者：
Lowry CA
影响因子：
14.8
作者：
Vang, Torkel;Liu, Wallace H.;Delacroix, Laurence;Wu, Shuangding;Vasile, Stefan;Dahl, Russell;Yang, Li;Musumeci, Lucia;Francis, Dana;Landskron, Johannes;Tasken, Kjetil;Tremblay, Michel L.;Lie, Benedicte A.;Page, Rebecca;Mustelin, Tomas;Rahmouni, Souad;Rickert, Robert C.;Tautz, Lutz
通讯作者：
Tautz, Lutz