Discovery of targeting ligands for breast cancer cells using the one-bead one-compound combinatorial method

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

Research output: Contribution to journalArticle

64 Scopus citations


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 a3 integrin was identified. Molecular 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 (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 (IC 50 = 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.

Original languageEnglish (US)
Pages (from-to)126-133
Number of pages8
JournalJournal of Medicinal Chemistry
Issue number1
StatePublished - Jan 8 2009


ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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