Optimization of RGD-Containing Cyclic Peptides against ?v?3 Integrin.

ABSTRACT: We have previously reported the use of one-bead-one-compound (OBOC) combinatorial technology to develop a disulfide cyclic, Arg-Gly-Asp-containing octapeptide LXW7 (cGRGDdvc), that targets ?v?3 integrin with high affinity and specificity. ?v?3 integrin is known to be overexpressed in many cancers and in tumor vasculature, and it has been established as a cancer therapeutic target. To further optimize LXW7, we have performed systematic structure-activity relationship studies. On the basis of the results, two highly focused OBOC peptide libraries were designed, synthesized, and screened against ?v?3 integrin-transfected K562 cells. One of the best ligands, LXW64, was found to have 6.6-fold higher binding affinity than LXW7, and showed preferential binding to cells expressing ?v?3 integrin. In addition to binding strongly to U-87MG glioblastoma cells in vitro, LXW64 also targets U-87MG xenografts implanted in nude mice, indicating that it is an excellent vehicle for the delivery of cytotoxic payload to tumors and tumor blood vessels that overexpress ?v?3 integrin. Mol Cancer Ther; 15(2); 232-40. ©2015 AACR.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC4747864 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature