Requirment driven protein design for nano targeting drug production

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15096
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 27040:Biofunction and bioprocess engineering-related
• Research Institution: Osaka University
• Principal Investigator: Niide Teppei 大阪大学, 情報科学研究科, 助教 (20802705)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: タンパク質工学 / 計算科学 / 低分子医薬

Outline of Final Research Achievements

This project expanded the recognition target of material-recognition biomolecules to self-assemblies of small-molecule drugs, aiming to create "nano-targeting drugs" as a new pharmaceutical format. Within the period of this project, we worked on the acquisition of nanomaterial-binding peptides using the phage display technique and the design of nanomaterial-binding proteins using Rosetta software. As a result, we obtained a peptide molecule that binds to the drug crystal surface with a dissociation constant of 99.7 nM and a maximum adsorption capacity of 344.8 pmol/mg. The peptide molecule was fused to a small binding protein that recognizes a cancer antigen on a computer using Rosetta software. The insertion position of the peptide molecule was searched for without a significant increase in the Rosetta energy unit, which indicates the stability energy value of the complete protein.

Free Research Field

タンパク質工学

Academic Significance and Societal Importance of the Research Achievements

抗体医薬と低分子医薬を化学修飾により組み合わせた抗体-薬物複合体(ADC)は、様々な疾患に対し副作用の無い医薬品として注目を集めているが、抗体の失活や不溶化が原因となり、高い確率で臨床試験以前で脱落してしまう。それに対し我々の目指したナノ分子標的薬は、これまでに無い新しい分子標的薬であり、学術的意義は大きい。さらに、このナノ分子標的薬で用いる人工タンパク質は、分子標的機能と薬剤ナノ粒子表面に結合する二つの機能に限定した低分子量タンパク質であるため、バクテリアで調製でき、薬価を大きく低減させることが期待できる。以上より、将来に向けた新しい創薬モダリティとして期待できる。