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.

中文翻译：

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Grb2 SH2 结构域信号拮抗剂的开发：一种潜在的新型抗增殖剂。

通过蛋白质酪氨酸激酶 (PTK) 依赖途径的异常信号传导与多种增殖性疾病有关。因此，正在开发 PTK 抑制剂作为治疗某些癌症的新方法。生长因子受体结合蛋白 2 (Grb2) 是 PTK 信号转导的重要下游介质，在许多致病过程中起着强制性作用。Grb2 的主要功能之一是通过其 Src 同源 2 (SH2) 域与特定的含磷酸酪氨酰 (pTyr) 的序列结合。与 Grb2 SH2 结构域结合并阻止其正常功能的药剂可能会破坏相关的 PTK 信号传导并作为激酶导向抑制剂的替代品。从与 Grb2 SH2 结构域结合的先导肽的 X 射线晶体结构开始，本综述将总结对这些工作的重要贡献。