A novel small peptide as a targeting ligand for receptor tyrosine kinase Tie2

作者：Wu, XH; Zhao, RJ; Li, ZH; Yao, M; Wang, HM; Han, JS; Qu, SM; Chen, XL; Qian, LF; Sun, Y; Xu, YH; Gu, JR^*

来源：Biochemical and Biophysical Research Communications, 2004, 315(4): 1004-1010.

DOI：10.1016/j.bbrc.2004.01.157

• Tie2
• angiogenesis
• peptide ligand
• tumor targeting
• angiopoietin-2

Tie2 is an endothelium-specific receptor tyrosine kinase known to play an important role in tumor angiogenesis. We sought to identify a small peptide ligand against Tie2 for developing a delivery targeting agent. We used hydrophobic analysis and comparative sequence/structure analysis to select a minimal peptide based on angiopoietin-2 amino acid sequence. The resulting peptide named GA3(WTIIQRREDGSVDFQRTWKEYK) was synthesized and labeled with iodine-125 at the C-terminal tyrosine residue to characterize its binding capability. In in vitro binding assays, GA3 can not only specifically bind to SMMC7721-Tie2 but also compete with angiopoietin-2 in binding. Via mouse tail vein injection, I-125-labeled GA3 was found to favorably accumulate in SPC-A1 xenograft tumor tissues which positively express Tie2. These results demonstrated that GA3 may be useful as a drug or gene delivery ligand for targeted chemotherapy, radiotherapy, and gene therapy.

• 出版日期2004-3-19
• 单位上海市肿瘤研究所; 上海交通大学; 复旦大学