Design of Humanized Adaptor Proteins Exhibiting Albumin-Binding Affinity

2016 Fiscal Year Final Research Report

• Project/Area Number: 26350968
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomolecular chemistry
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Honda Shinya 国立研究開発法人産業技術総合研究所, バイオメディカル研究部門, 副研究部門長 (50344122)
• Co-Investigator(Renkei-kenkyūsha): WATANABE Hideki 産業技術総合研究所, バイオメディカル研究部門, 主任研究員 (90422089)
• Research Collaborator: OSHIRO Satoshi 東京大学, 大学院・新領域創成科学研究科メディカルゲノム専攻, 大学院生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 分子設計 / バイオテクノロジー / バイオ医薬品 / タンパク質工学 / 薬物動態 / 血中安定性 / ヒト血清アルブミン

Outline of Final Research Achievements

Attachment of a bacterial albumin-binding protein module is an attractive strategy for extending the plasma residence time of protein therapeutics. However, a protein fused with such a bacterial module could induce unfavorable immune reactions. To address this, we designed an alternative binding protein by imparting albumin-binding affinity to a human protein using molecular surface grafting. One of the designed proteins using human-derived 6 helix-bundle scaffold specifically binds to human serum albumin with adequate affinity. Despite 13-15 mutations, the designed proteins maintain the original secondary structure by virtue of careful grafting based on structural informatics. Competitive binding assays and thermodynamic analyses of the best binders show that the binding mode resembles that of the original bacterial protein module, suggesting that the contacting surface is mimicked well on the designed protein.

Free Research Field

ケミカルバイオロジー