The molecular analysis of the structural basis of Notch1/Dll4 interaction for drug discovery.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07330
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Tokai University
• Principal Investigator: Hozumi Katsuto 東海大学, 医学部, 教授 (30246079)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Notch / Dll4 / Dll1 / 胸腺

Outline of Final Research Achievements

To understand the characteristics of the binding between Dll4 and Notch1, we investigate the structure and function of the swapping chimeras of Dll1 and Dll4. Dll4 has unique two AA neighbored to DSL region, in addition to the use of MNNL region for its binding to Notch1. These must be main targets for the specific manipulation of Dll4/Notch1 binding.

Free Research Field

医化学

Academic Significance and Societal Importance of the Research Achievements

Notchシステムは、腫瘍化をはじめ様々な生命現象に寄与するが、すべてのNotch/NotchLの機能を抑制することにより強い副作用が生じ、治療への応用が困難である。本研究では、代表的なNotchLであるDll4の特徴的構造およびその機能に着目し、Dll4の機能を特異的に抑制するための基礎となるNotch1との結合特性を明らかにした。