Synthesis of Multi-functional Peptide Conjugates

2019 Fiscal Year Final Research Report

• Project Area: Middle molecular strategy: Creation of higher bio-functional molecules by integrated synthesis.
• Project/Area Number: 15H05843
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Tanaka Katsunori 国立研究開発法人理化学研究所, 開拓研究本部, 主任研究員 (00403098)
• Project Period (FY): 2015-06-29 – 2020-03-31
• Keywords: 中分子 / 生体内合成 / 糖鎖 / ペプチド / がん細胞 / マウス

Outline of Final Research Achievements

We developed a pre-targeted method by which target cells could be selectively imaged using a labeled N-glycan that was ligated in situ with a high-affinity peptide ligand on the cell surface. We demonstrated the power of this method in discriminating various cancer and non-cancerous cells that cannot be distinguished using conventional integrin-targeted paptide ligands. Using various integrin-targeted peptides and N-glycans with various linker lengths, we identified optimal combinations to discriminate several types of integrin–expressing cells on 96-well plates. The optimal combinations of peptide and N-glycan ligands for the target cells were fingerprinted on the plates, and then used to selectively image tumors in xenografted mouse models. Using this method, various N-glycan molecules, even those with millimolar affinities for their cognate lectins, could be used for selective cancer cell differentiation.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

ヒトや動物などの生体内分子イメージングは、抗がん剤の体内動態や特定の疾患細胞の診断方法として注目されている。しかし現在でも、実際の患者では、様々ながんや疾患の種類を高感度・高選択性で見分けることは難しい。本課題で報告者が開発した2種類のリガンド分子を組み合わせて標的細胞上の複数の受容体を認識・生体内合成する技術を応用することで、今後、生体内のがん組織や疾患部位を選択的に識別することができる新たな診断方法の開発が期待できる。