Structure–activity study and analysis of mechanism of action of vibsanins focused on pro-/anti-inflammatory switching

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K05846
• 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: Kagawa University
• Principal Investigator: Yanagita Ryo 香川大学, 農学部, 准教授 (10598121)
• Co-Investigator(Kenkyū-buntansha): 川浪 康弘 香川大学, 農学部, 教授 (30169742)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: プロテインキナーゼC / 構造活性相関 / 分子動力学シミュレーション

Outline of Final Research Achievements

Vibsanin A, a protein kinase C (PKC) activator isolated from Viburnum odoratissimum tree, was found to have about 4000-fold binding selectivity between PKCα-C1A and δ-C1B domains, which is the highest among known PKC ligands. Molecular dynamics simulation presented the binding mode of vibsanin A with the PKCδ-C1B domain, wherein CH-O interactions are involved. LC-MS analysis suggested that the chemical instability of vibsanin A is attributable to its susceptibility to oxidation. Furthermore, we found that (8Z)-5,10-di-epi-vibsanin C (vibsanin D), not vibsanin C, has the potential as a lead scaffold for developing novel PKC ligands.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

Vibsanin AのPKC結合活性と化学的安定性についての基礎的な知見は、今後vibsaninの作用機序解析や誘導体開発を行ううえでの基盤となる。PKC活性化剤はがん、アルツハイマー病、HIV感染などの治療薬候補として研究が行われており、vibsanin類やその誘導体・アナログはこういった疾患に対する治療薬開発のリードとして有望である。