Therapeutic In Vivo Synthetic Chemistry by Transition Metal Catalyzed Amidation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H03287
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomolecular chemistry
• 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): 2016-04-01 – 2019-03-31
• Keywords: 化学合成 / 生体分子 / 蛋白質 / 糖鎖 / 生体内合成化学治療

Outline of Final Research Achievements

If we could synthesize these drug candidates at the disease tissue directly in vivo, potential benefits are that side effects to other organs may be lessened and the therapeutic window of drug activity can be prolonged before decomposition. We referred to this new clinical approach as "Therapeutic In Vivo Synthetic Chemistry".
One promising strategy is to use transition metal catalyzed reaction in vivo. We developed new metal-catalyzed (or mediated) transformations in biologically relevant media. To perform this reaction selectively in vivo at targeted organs, we designed a strategy that conjugates transition metal catalysts to glycoclusters, which quickly and selectively accumulate to target organs. Following injection of these metal conjugated glycoclusters into mice, we then injected the reagents to label or synthesizing the molecules at the targeted organs in mice. Our strategy led to the first example of organ selective metal catalyzed reactions.

Free Research Field

生体合成化学

Academic Significance and Societal Importance of the Research Achievements

報告者らが開発した方法を用いて狙った臓器で選択的に金属触媒反応を起こせば、がんなどの疾患部位で、直接、薬などの生理活性分子を合成できると期待できる。さまざまな金属触媒反応に展開できると考えられ、体内で薬の合成が可能となる。その結果、薬が疾患部位以外で作用して起きる副作用の問題、あるいはペプチドなど不安定な薬の体内での安定性の問題を解決できると期待できる。過去、ドロップアウトしてきた薬理活性分子を生体内で直接見直す新戦略であり、創薬化学やプロドラッグ、あるいはドラッグデリバリーシステムにおける「分子機能のルネッサンス」となる。