Development of highly sensitive peptide probes with optimized kinetics based on cross-linking method

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17212
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Osaka Medical and Pharmaceutical University (2021); Osaka University of Pharmaceutical Sciences (2019-2020)
• Principal Investigator: Kondo Naoya 大阪医科薬科大学, 薬学部, 助教 (80756172)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ペプチド / 安定化 / イメージングプローブ

Outline of Final Research Achievements

In this study, we proposed a new method for developing peptide probes, focusing on a method to control degradation of unstable peptides by cross-linking to extend their in vivo half-life. This method can solve the difficulty of controlling the kinetics of peptide probes and the problem of separation and purification after radiolabeling. In this study, we selected the unstable peptide GLP-1 and the bicyclic RGD peptide as models, performed in vitro and in vivo experiments on the synthesized imaging probes ([125I]GLP-1CL and [125I]bcRGD), and validated the effectiveness of this method. We found that the cross-linked peptides have excellent properties as imaging probes. The results of this study are expected to contribute to the development of peptide chemistry and diagnostic and therapeutic research.

Free Research Field

分子イメージング

Academic Significance and Societal Importance of the Research Achievements

ペプチドは高い標的認識性を有し、核医学領域でも診断用・治療用のプローブとして有効性が認められている。一方で、生体内での不安定性が動態に影響し、放射標識後の精製が困難であるなど中分子であるペプチド特有の性質が診断薬・治療薬の開発難度を高めており、有効な動態制御法、精製法の確立がペプチド性プローブ開発の発展に不可欠である。ペプチドへの架橋構造に放射標識部位を組み入れる本手法の有効性を明らかにした本課題の成果は、治療・診断を一体化するセラノスティクス用薬剤開発や、長期滞留型の治療薬開発の可能性に直結し、ペプチド化学や診断・治療研究、個別化医療の発展に幅広く貢献すると考える。