Details

Autor(en) / Beteiligte

• Yao, Nianhuan
• Xiao, Wenwu
• Wang, Xiaobing
• Marik, Jan
• Park, See Hyoung
• Takada, Yoshikazu
• Lam, Kit S

Titel

Discovery of Targeting Ligands for Breast Cancer Cells Using the One-Bead One-Compound Combinatorial Method

Ist Teil von

• Journal of medicinal chemistry, 2009-01, Vol.52 (1), p.126-133

Ort / Verlag

Columbus, OH: American Chemical Society

Erscheinungsjahr

2009

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Four “one-bead one-compound” (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 α3 integrin was identified. Molecular interactions between α3 integrin and 1 were characterized by using a series of K562 cells transfected with various mutant α3 integrins. Using analytic flow cytometry, the binding affinity (K d) of 1 to α3 integrin on MDA-MB-231 breast cancer cells was determined to be approximately 0.4 μM. 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-infrared fluorescence optical imaging.