Directed evolution of cyclized N-alkyl peptides targeted to cellular biomolecules

2015 Fiscal Year Final Research Report

• Project/Area Number: 25870146
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology; Bio-related chemistry
• Research Institution: National Institute of Advanced Industrial Science and Technology (2014-2015); The University of Tokyo (2013)
• Principal Investigator: Kawakami Takashi 国立研究開発法人産業技術総合研究所, 創薬分子プロファイリング研究センター, 研究員 (60638881)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: PUREシステム / mRNAディスプレイ / Nメチルペプチド / Elongation factor P / 分子進化 / ペプトイド / Nアルキルペプチド / プロテオミクス

Outline of Final Research Achievements

By the addition of elongation factor P (EF-P) to an E. coli reconstituted cell-free translation system, PURE system (Protein-synthesis Using Recombinant Elements systen), we successfully evaluated translation efficiency of cyclic N-alkyl amino acids in a library of mRNA-displayed highly N-alkylated polycyclic peptidomimetics.
By using bio-orthognal chemical reaction or enzymatic reaction, we developed a novel method to incorporate electorically-charged N-alkyl amino acids to ribosomally synthesized peptides.
By combining the PURE system with an mRNA display method, we successfully in vitro-evolved cyclized N-alkyl peptides targeted to VEGFR2 expressed in living human cells.

Free Research Field

ケミカルバイオロジー・生体関連化学