Fluorophore Labeling Enables Imaging and Evaluation of Specific CXCR4−Ligand Interaction at the Cell Membrane for Fluorescence-Based Screening

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• 作者：Wataru Nomura ; Yasuaki Tanabe ; Hiroshi Tsutsumi ; Tomohiro Tanaka ; Kenji Ohba ; Naoki Yamamoto ; Hirokazu Tamamura
• 刊名：Bioconjugate Chemistry
• 出版年：2008
• 出版时间：September 17, 2008
• 年：2008
• 卷：19
• 期：9
• 页码：1917-1920
• 全文大小：195K
• 年卷期：v.19,no.9(September 17, 2008)
• ISSN：1520-4812

文摘

Development of CXCR4-specific ligands is an important issue in chemotherapy of HIV infection, cancer metastasis, and rheumatoid arthritis, and numerous potential ligands have been developed to date. However, it is difficult to assess their binding mode and specificity because of uncertainties in the structure of the CXCR4−ligand complexes. To address this problem, we have synthesized fluorophore labeled Ac-TZ14011, which is derived from T140, a powerful CXCR4 antagonist. Binding of Ac-TZ14011 to CXCR4 on the cell membrane was observed by fluorescence microscope, and analysis of the binding data produced IC₅₀ values of several ligands comparable to those obtained in RI-based assays. This fluorescence-based assay is applicable to explore new pharmacophores of CXCR4-specific ligands with high-throughput screening and also to screening of the other GPCR binding ligands.