2021 Fiscal Year Final Research Report
N-terminal modification of peptides by selective formation of azomethine ylides
| Project/Area Number |
20K15288
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 33020:Synthetic organic chemistry-related
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| Research Institution | Tohoku University (2021)
Chuo University (2020) |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | ペプチド / アゾメチンイリド / N-末端 / 環化付加反応 / クリックケミストリー |
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| Outline of Final Research Achievements |
Peptide modification is an important method for drug conjugation, bioimaging, and material development. However, site selective modification of peptides is still challenging owing to the existence of several reaction sites and interactions. Recently, N-terminal modification of peptides has attracted increasing attention as a site selective modification, because there is only one N-terminal residue in a peptide. In addition, N-terminal positions are accessible for chemical modification, and disruption of peptide conformation is minimal. Despite their utility, the present N-terminal modification causes some problems, such as equilibrium dissociation.
In this study, we developed an N-terminal modification of peptides by applying metal-catalyzed 1,3-dipolar cycloaddition, leading to a strong C-C bond. The reaction proceeded efficiently to achieve excellent diastereoselectivity to afford the corresponding pyrrolidine derivatives.
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| Free Research Field |
有機合成化学
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| Academic Significance and Societal Importance of the Research Achievements |
ペプチド構造はタンパク質などを構成する重要な構造であり，イメージングや機能性分子の創出などの観点から修飾法の開発が求められている．一方で，多彩な反応点や相互作用が存在することから，位置や個数選択的に修飾を行うのは未だ容易ではなかった．
これに対して，本研究課題では，1,3-双極子のアゾメチンイリドを，通常１カ所しかないN-末端のみで選択的に発生させられることを明らかにし，これを環化付加反応に効率的に利用することに成功した．本手法は，位置選択的な新たなペプチド修飾法として，ペプチドへの蛍光分子などの機能性分子の選択的な連結を可能にするため，多彩な生命科学研究への利用が期待される．
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