Creation of novel Catalytide with In Silico

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22499
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Kochi University
• Principal Investigator: Akizawa Toshifumi 高知大学, 医学部, 特任教授 (30202526)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: Catalytide / アルツハイマー病 / 神経変性疾患 / 酵素ペプチド / ALS / パーキンソン病

Outline of Final Research Achievements

To find the novel Catalytide in Silico, we analyzed the stereo-structure of Catalytides by Personal Computer (PC)with MM2 and MMFF94 parameters. As the results, we determined the active center amino acid and stereo-structure required for activity. We next tried to identify the novel Catalytide. We applied our finding to 5-mer Catalytide, GSGHR, that the most effective protease against Aβ11-29 and several kinds of that derivatives including D-amino acid in the molecule. As the results, we identified the novel Catalytide. This study indicated that Catalytide can be created with ease in Silico by PC with MM2 and MMFF94 parameters without supercomputer. We are now trying to the novel Catalytide being applicable for SARS-CoV-2 spike.

Free Research Field

分析科学

Academic Significance and Societal Importance of the Research Achievements

Catalytide は新規性が極めて高く、特に5 残基ペプチドは誘導体も含め合成は極めて簡単で、PC による構造解析も酵素タンパク質と異なり短時間でできる。申請者らの保有する 70 種を超える 5 残基ペプチドの立体構造を PC で解析し、酵素活性に必要なアミノ酸の空間的位置関係を解析することで、新規 Catalytide の創造が可能となる。本研究の成果は、これまでの治療薬とは全くストラテジーの異なった日本発の根本的なアルツハイマー病治療薬の開発のみでなく、凝集性タンパク質が発症原因となるパーキンソン病、ALS、プリオン、IgA 腎症などの治療薬開発に繋がることも期待できる。