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2023 Fiscal Year Final Research Report

Discovery and validation of high-performance recombinant ligands

Research Project

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Project/Area Number 21K18250
Research Category

Grant-in-Aid for Challenging Research (Pioneering)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 48:Biomedical structure and function and related fields
Research InstitutionKanazawa University

Principal Investigator

Matsumoto Kunio  金沢大学, がん進展制御研究所, 教授 (90201780)

Co-Investigator(Kenkyū-buntansha) 井上 啓  金沢大学, 新学術創成研究機構, 教授 (50397832)
Project Period (FY) 2021-07-09 – 2024-03-31
Keywords環状ペプチド / Lasso-Graft / HGF / MET / 細胞増殖因子
Outline of Final Research Achievements

The aim of this study was to obtain super-functional biologics using cyclic peptide-based Lasso-Graft protein engineering technology. We succeeded in creating a highly blood-stable "HGF (Hepatocyte Growth Factor)-mimetic" aMD4-Fc which induces dimerization and activation of the MET receptor, by interpolating MET-binding aMD4 cyclic peptide sequence into IgG Fc. Furthermore, by interpolating aMD4 into the Fc region of anti-transferrin antibody that cross the blood-brain barrier/BBB, we succeeded in creating a super-functional molecule that reaches neurons in the brain parenchyma as well as having MET-activating ability (Nature Biomed Eng, 2023).

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

細胞増殖因子は顕著な生理活性をもつが、医薬としての化学特性が不十分で、医薬として利用される増殖因子は一部にとどまる。したがって、細胞増殖因子と同等の生理活性をもつとともに、血中安定性や血液脳関門移行能といった優れた特性を併せもつ分子は画期的医薬になる。本研究では環状ペプチドを基盤とする分子技術Lasso-Graft法を、HGF-MET受容体系に応用し、長期の血中安定性とHGFと同等のMET活性化能を併せもつ分子、血液脳関門移行能とMET活性化能を併せもつ分子を創成することに成功した。これらは顕著な生物活性と医薬としての高い性能を兼ね備えており、さまざまな難治性疾患の治療医薬になると期待される。

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Published: 2025-01-30  

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