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生长因子受体结合蛋白2(Grb2)在致癌基因Ras活化的信号传导通路中起着关键作用,目前被广泛认为是抗肿瘤药物设计的优秀靶标.对Grb2-SH2抑制剂的研究进展进行了综述,主要针对关键残基磷酸酪氨酸的高电荷性和多肽结构的低生物相容性两个缺陷,基于天然配体与Grb2-SH2相互作用的结构特征,围绕提高活性和简化结构开展的系统构效关系和合理结构优化研究,为进一步开发磷酸酪氨酸介导的Grb2-SH2抑制剂成为新型抗肿瘤药物提供结构和理论基础.
Growth factor receptor binding protein 2 (Grb2) plays a key role in the oncogene Ras-activated signal transduction pathway and is now widely recognized as an excellent target for antitumor drug design. The progress of Grb2-SH2 inhibitors is reviewed , Mainly focusing on the two defects of the high charge of the key residue phosphotyrosine and the low biocompatibility of the polypeptide structure. Based on the structural characteristics of the interaction between the natural ligand and Grb2-SH2, the system around the activity of increasing activity and simplifying the structure Structure-activity relationship and rational structure optimization research, which will provide the structural and theoretical basis for the further development of the phosphotyrosine-mediated Grb2-SH2 inhibitor as a novel antitumor drug.