Highly Efficient Synthesis of ADP-Ribosylated Peptides by Protecting Group Free Segment Coupling Methods

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K05461
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38040:Bioorganic chemistry-related
• Research Institution: Gifu University
• Principal Investigator: Tanaka Hidenori 岐阜大学, 糖鎖生命コア研究所, 助教 (20725064)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ADPリボース / 無保護合成 / ピロリン酸

Outline of Final Research Achievements

ADP ribosylation, one of post-translational modifications, is a reaction that transfers ADP ribose from nicotinamide adenine dinucleotide (NAD+) to proteins and plays an important role in a variety of cellular processes including DNA repair and transcriptional regulation. Its biological importance has widely been investigated but detailed functions of ADP ribosylation remain poorly understood. The main difficulty in the molecular level research is to obtain homogeneous ADP ribosylated molecules. In this study, we develop a highly efficient method for synthesis of ADP ribosyl molecules. We established protecting-free pyrophosphate formation by phosphate cross-coupling reaction and applied it to chemical synthesis of mono- and di-ADP riboses.

Free Research Field

生物有機化学

Academic Significance and Societal Importance of the Research Achievements

ADPリボシル化の分子レベル機能解明研究のボトルネックは、構造均一な分子の量的供給であった。本研究では、リン酸クロスカップリング反応でピロリン酸結合を効率的に形成できることを実証し、ADPリボシル化分子の高効率合成法の開発の糸口を見出した。合成基盤の確立は分子の量的供給が可能とするため、ADPリボシル化の機能だけでなく、生物学的意義の解明に今後大きく貢献することが期待できる。