Development of early diagnostic methods for cancer tissue and metastasis utilizing bivalent GPCR ligands

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390024
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TAMAMURA HIROKAZU 東京医科歯科大学, 生体材料工学研究所, 教授 (80217182)
• Co-Investigator(Kenkyū-buntansha): NOMURA Wataru 東京医科歯科大学, 生体材料工学研究所, 准教授 (80463909) ; NARUMI Testuo 東京医科歯科大学, 生体材料工学研究所, 助教 (50547867) ; AIKAWA Haruo 東京医科歯科大学, 生体材料工学研究所, 特任助教 (70547322)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 分子標的 / GPCR / 分子プローブ / 創薬ツール / ケモカインレセプターCXCR4 / ２価結合型リガンド / 認識ユニット / がん

Outline of Final Research Achievements

The assembly status of G protein-coupled receptors (GPCR) on the cellular surface is of interest because the multimerization of GPCR could play pivotal roles in cellular functions. A bivalent ligand with polyproline linkers for CXCR4 has been shown to serve as “molecular ruler” as a result of the rigid structure of polyproline helices. To expand the utility of the ligands with rigid linkers and explore the possible multimeric forms of GPCR, ligands with polyproline helices were newly designed and synthesized. The binding affinities of ligands for CXCR4 suggested that the ligands recognize the dimeric form of CXCR4 on the cellular surface. The fluorescent imaging and analysis by flow cytometry revealed that the ligand with 9-proline linkers binds to CXCR4 with remarkable specificity. The results of the present study suggest that the ligand design with rigid linkers is useful in the multimeric form.

Free Research Field

ケミカルバイオロジー、創薬化学