An ultrahigh affinity d-peptide antagonist Of MDM2.
An ultrahigh affinity d-peptide antagonist Of MDM2.
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DOI：
10.1021/jm3005465
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发表时间：
2012-07-12
影响因子：
7.3
通讯作者：
Lu, Wuyuan
中科院分区：
文献类型：
--
作者：
Zhan, Changyou;Zhao, Le;Wei, Xiaoli;Wu, Xueji;Chen, Xishan;Yuan, Weirong;Lu, Wei-Yue;Pazgier, Marzena;Lu, Wuyuan
The oncoprotein MDM2 negatively regulates the activity and stability of the p53 tumor suppressor, and is an important molecular target for anticancer therapy. Aided by mirror image phage display and native chemical ligation, we have previously discovered several proteolysis-resistant duodecimal D-peptide antagonists of MDM2, termed DPMI-α, β, γ. The prototypic D-peptide inhibitor DPMI-α binds (25-109)MDM2 at an affinity of 220 nM, and kills tumor cells in vitro and inhibits tumor growth in vivo by reactivating the p53 pathway. Herein, we report the design of a super-active D-peptide antagonist of MDM2, termed DPMI-δ, of which the binding affinity for (25-109)MDM2 has been improved over DPMI-α by three orders of magnitude (Kd = 220 pM). X-ray crystallographic studies validate DPMI-δ as an exceedingly potent inhibitor of the p53-MDM2 interaction, promising to be a highly attractive lead drug candidate for anticancer therapeutic development.
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影响因子：
64.5
作者：
Eckert, DM;Malashkevich, VN;Kim, PS
通讯作者：
Kim, PS
影响因子：
56.9
作者：
DAWSON, PE;MUIR, TW;KENT, SBH
通讯作者：
KENT, SBH
p53 抑制剂 MDM2/MDMX 复合物是控制体内 p53 活性所必需的
DOI：
10.1073/pnas.1102309108
发表时间：
2011-07-19
影响因子：
11.1
作者：
Huang, Lei;Yan, Zheng;Yuan, Zhi-Min
通讯作者：
Yuan, Zhi-Min
影响因子：
15
作者：
Bilgiçer, B;Fichera, A;Kumar, K
通讯作者：
Kumar, K
影响因子：
3.2
作者：
Hintersteiner, Martin;Kimmerlin, Thierry;Auer, Manfred
通讯作者：
Auer, Manfred