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 S. Lam

研究成果: 雜誌貢獻文章同行評審

65 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)126-133
頁數8
期刊Journal of Medicinal Chemistry
52
發行號1
DOIs
出版狀態已發佈 - 一月 8 2009

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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