2022 Fiscal Year Final Research Report
Synthesis and Medicinal Chemical Development of Mid-Sized Peptide Conjugate Based on the Chemistry of Solid-Phase Disulfide Ligation
| Project/Area Number |
19H03356
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
|
|---|
| Research Institution | Tokyo University of Pharmacy and Life Science |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
田口 晃弘 東京薬科大学, 薬学部, 講師 (40707311)
|
|---|
| Project Period (FY) |
2019-04-01 – 2023-03-31
|
| Keywords | 固相ジスルフィドライゲーション / 中分子ペプチド / ペプチドー薬物複合体 / 創薬 / ケミカルバイオロジー / ペプチド化学 / ジスルフィド結合 / 有機合成 |
|---|
| Outline of Final Research Achievements |
Focusing on the synthesis of conjugates, i.e., combined molecules with different functions, which are one of the common platforms for next-generation mid-sized peptide drugs, we conducted a verification of the usefulness of the solid-phase disulfide ligation (solid-phase DSL) method. The solid-phase DSL is originally developed by our group as a novel construction method for such cross-linked molecules. In other words, this study aimed to develop disulfide-directed peptide synthetic chemistry based on solid-phase DSL, to create novel 'functional molecules' including medium-sized peptide conjugates, and to develop their drug discovery. Specifically, The project performed to develop synthetic methods for new disulfide peptides and multiple disulfide artificial proteins by solid-phase DSL. The project also focused on drug discovery research based on the development of functional conjugates such as peptide-drug conjugates (PDCs) and antibody-peptide-drug crosslinkers (APDCs).
|
| Free Research Field |
創薬科学
|
| Academic Significance and Societal Importance of the Research Achievements |
本課題では、独自に開発した固相ジスルフィドライゲーション (固相DSL) を学術的基盤として、新規なジスルフィド先導型ペプチド合成法を創製し、それを利用した中分子ペプチド架橋体を含む新規機能分子の創製を成し遂げた。その中で固相DSLで利用する一部Npys誘導体は試薬として市販され、さらに新規水溶性Npys誘導体の開発にも成功、複雑な環状ペプチドの合成や固相上での環状ペプチドの完全自動合成を成し遂げ、さらにペプチド主鎖にジスルフィド結合を複数有するタンパク質合成や新規架橋体の構築に基づく抗がん剤創製研究への展開を実施できた。これらにより、固相DSLの創薬における重要性を示すことができた。
|
