TY - JOUR
T1 - Discovery of targeting ligands for breast cancer cells using the one-bead one-compound combinatorial method
AU - Yao, Nianhuan
AU - Xiao, Wenwu
AU - Wang, Xiaobing
AU - Marik, Jan
AU - Park, See Hyoung
AU - Takada, Yoshikazu
AU - Lam, Kit S.
PY - 2009/1/8
Y1 - 2009/1/8
N2 - 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.
AB - 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.
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U2 - 10.1021/jm801062d
DO - 10.1021/jm801062d
M3 - Article
C2 - 19055415
AN - SCOPUS:59449089842
SN - 0022-2623
VL - 52
SP - 126
EP - 133
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 1
ER -