Development of Grb2 SH2 Domain Signaling Antagonists: A Potential New Class of Antiproliferative Agents.
Development of Grb2 SH2 Domain Signaling Antagonists: A Potential New Class of Antiproliferative Agents.
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DOI：
10.1007/s10989-006-9014-7
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发表时间：
2006-03
影响因子：
2.5
通讯作者：
Burke, TR
中科院分区：
文献类型：
--
作者：
Burke, TR
通过蛋白酪氨酸激酶（PTK）依赖性途径的异常信号传导与几种增殖性疾病相关。因此，PTK抑制剂正被开发为用于治疗某些癌症的新方法。生长因子受体结合蛋白2（Grb 2）是PTK信号传导的重要下游介质，在许多致病过程中起强制性作用。Grb 2的主要功能之一是通过其Src同源2（SH 2）结构域与特定的含磷酸酪氨酸（pTyr）的序列结合。与Grb 2 SH 2结构域结合并阻止其正常功能的药物可能会破坏相关的PTK信号传导，并可作为激酶导向抑制剂的替代品。从X-射线晶体结构的铅肽绑定到Grb 2 SH 2域，这篇评论将总结这些努力的重要贡献。介绍将根据修饰的肽的区域按主题排列，从N-末端到C-末端，其中一个特殊部分专门用于构象约束方面。
Aberrant signaling through protein-tyrosine kinase (PTK)-dependent pathways is associated with several proliferative diseases. Accordingly, PTK inhibitors are being developed as new approaches for the treatment of certain cancers. Growth factor receptor bound protein 2 (Grb2) is an important downstream mediator of PTK signaling that serves obligatory roles in many pathogenic processes. One of the primary functions of Grb2 is to bind to specific phosphotyrosyl (pTyr)-containing sequences through its Src homology 2 (SH2) domain. Agents that bind to the Grb2 SH2 domain and prevent its normal function could disrupt associated PTK signaling and serve as alternatives to kinase-directed inhibitors. Starting from the X-ray crystal structure of a lead peptide bound to the Grb2 SH2 domain, this review will summarize important contributions to these efforts. The presentation will be thematically arranged according to the region of peptide modified, proceeding from the N-terminus to the C-terminus, with a special section devoted to aspects of conformational constraint.
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影响因子：
64.8
作者：
ECK, MJ;SHOELSON, SE;HARRISON, SC
通讯作者：
HARRISON, SC
影响因子：
7.3
作者：
Ettmayer, P;France, D;Bair, KW
通讯作者：
Bair, KW
影响因子：
7.3
作者：
Furet, P;Gay, B;Caravatti, G
通讯作者：
Caravatti, G
DOI：
10.1016/s0006-291x(03)01291-9
发表时间：
2003-08-08
影响因子：
3.1
作者：
Li, P;Zhang, MC;Roller, PP
通讯作者：
Roller, PP
影响因子：
2.7
作者：
Caravatti, G;Rahuel, J;Furet, P
通讯作者：
Furet, P