A novel small peptide as a targeting ligand for receptor tyrosine kinase Tie2.
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, 125I-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.
National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao-Tong University Medical School, Shanghai 200032, PR China.
Xianghua
X
Wu
Ruijiao
R
Zhao
Zonghai
Z
Li
Ming
M
Yao
Huamao
H
Wang
Junsong
J
Han
Shumin
S
Qu
Xianlian
X
Chen
Lianfang
L
Qian
Ye
Y
Sun
Yuhong
Y
Xu
Jianren
J
Gu
D000595:Amino Acid Sequence; D042702:Angiopoietin-2 / Q000737:chemistry / Q000235:genetics; D000818:Animals; D001682:Biological Availability; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007150:Immunohistochemistry; D008024:Ligands; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011869:Radioligand Assay; D042787:Receptor, TIE-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020539:Sequence Analysis, Protein / Q000379:methods; D014018:Tissue Distribution
D042702:Angiopoietin-2; D008024:Ligands; D010455:Peptides; D042787:Receptor, TIE-2