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

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

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
Pages (from-to)126-133
Number of pages8
JournalJournal of Medicinal Chemistry
Volume52
Issue number1
DOIs
Publication statusPublished - Jan 8 2009
Externally publishedYes

Fingerprint

Integrins
Cyclic Peptides
Breast Neoplasms
Ligands
Optical Imaging
Peptide Library
K562 Cells
Structure-Activity Relationship
Heterografts
Flow Cytometry
Adenocarcinoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Discovery of targeting ligands for breast cancer cells using the one-bead one-compound combinatorial method. / Yao, Nianhuan; Xiao, Wenwu; Wang, Xiaobing; Marik, Jan; Park, See Hyoung; Takada, Yoshikazu; Lam, Kit S.

In: Journal of Medicinal Chemistry, Vol. 52, No. 1, 08.01.2009, p. 126-133.

Research output: Contribution to journalArticle

Yao, Nianhuan ; Xiao, Wenwu ; Wang, Xiaobing ; Marik, Jan ; Park, See Hyoung ; Takada, Yoshikazu ; Lam, Kit S. / Discovery of targeting ligands for breast cancer cells using the one-bead one-compound combinatorial method. In: Journal of Medicinal Chemistry. 2009 ; Vol. 52, No. 1. pp. 126-133.
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