[摘要]：Four "one-bead one-compd." (OBOC) combinatorial libraries were designed, synthesized, and screened against MDA-MB-231 breast cancer cells. A novel cyclic peptide 1 (LXY1) with high binding specificity to a3 integrin was identified. Mol. interactions between a3 integrin and 1 were characterized by using a series of K562 cells transfected with various mutant a3 integrins. Using analytic flow cytometry, the binding affinity (Kd) of 1 to a3 integrin on MDA-MB-231 breast cancer cells was detd. to be approx. 0.4 mM. Based on the established structure-activity relationship (SAR) study, two highly focused cyclic peptide libraries were further designed, synthesized, and screened against MDA-MB-231 breast cancer cells under stringent conditions. A novel cyclic peptide 2 (LXY3) with a high binding affinity (IC50 = 57 nM) was identified. Moreover, the targeting efficiency and specificity of 2 to the breast adenocarcinoma tumors in mouse xenografts were further confirmed by in vivo and ex vivo near-IR fluorescence optical imaging.
