Creation of novel hybrid catalysts by introducing a transition metal complex into an antigen binding site of monoclonal antibody

2019 Fiscal Year Final Research Report

• Project Area: Precise Formation of a Catalyst Having a Specified Field for Use in Extremely Difficult Substrate Conversion Reactions
• Project/Area Number: 15H05807
• 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: Osaka University
• Principal Investigator: Yamaguchi Hiroyasu 大阪大学, 理学研究科, 教授 (00314352)
• Project Period (FY): 2015-06-29 – 2020-03-31
• Keywords: モノクローナル抗体 / 遷移金属錯体 / 不斉触媒 / 立体選択性 / キラル誘起 / 配位子 / 炭素－炭素結合 / 光学活性

Outline of Final Research Achievements

Design and engineering of protein scaffolds are crucial to create artificial metalloenzymes. Herein we realized the first example of C-C bond formation catalyzed by artificial metalloenzymes, which consist of monoclonal antibodies (mAbs) and C2 symmetric metal catalysts. Prepared as a tailored protein scaffold for a binaphthyl derivative (BN), mAbs bind metal catalysts bearing a 1,1'-bi-isoquinoline (BIQ) ligand to yield artificial metalloenzymes. These artificial metalloenzymes catalyze the Friedel-Crafts alkylation reaction. In the presence of mAb, the reaction proceeds with 88% ee. The reaction catalyzed by Cu-catalyst incorporated into the binding site of mAb is found to show excellent enantioselectivity with 99% ee. The protein environment also enables the use of BIQ-based catalysts as asymmetric catalysts for the first time.

Free Research Field

生体機能関連化学

Academic Significance and Societal Importance of the Research Achievements

モノクローナル抗体が形成する特異なタンパク質空間に金属錯体を取り込むことにより、高度に制御された反応場を創製することに成功した。水中で不安定なパラジウム錯体を安定化させる、あるいはアキラルな銅錯体を取り込むことで不斉を誘起させるシステムを構築することができた。触媒ユニット近傍の環境を高分子とのハイブリッド化により厳密に制御できた。この経験を活かし、領域内共同研究を展開した結果、酵素の触媒活性を高分子ヒドロゲルの導入により自在に制御することも可能になった。