Enhancing the incorporation of lysine derivatives into proteins with methylester forms of unnatural amino acids

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:30

Article

Zhou, Han¹  Cheung, Jenny W.²  Carpenter, Tomaya¹  Jones, Stacey K., Jr.¹  Luong, Nhu H.¹  Tran, Nhi C.¹  Jacobs, Savannah E.¹  Liyanage, Sahan A. Galbada²  Cropp, T. Ashton^2,3  Yin, Jun¹ 

[1] Georgia State Univ, Ctr Diagnost & Therapeut, Dept Chem, Atlanta, GA 30302 USA

[2] Virginia Commonwealth Univ, Dept Chem, Box 2006, Richmond, VA 23284 USA

[3] Virginia Commonwealth Univ, Inst Struct Biol Drug Discovery & Dev, Richmond, VA 23219 USA

关键词: Unnatural amino acid;    Methyl ester;    Ubiquitin;    Aminoacyl-tRNA synthetase;    Protein expression;   

DOI  :  10.1016/j.bmcl.2019.126876

来源: Elsevier

【 摘 要 】

We have improved the incorporation of L- and D-forms of unnatural amino acid (UAA) N-epsilon-thiaprolyl-L-lysine (ThzK) into ubiquitin (UB) and green fluorescent protein (GFP) by 2-6 folds with the use of the methylester forms of the UAAs in E coli cell culture. We also improved the yields of UAA-incorporated UB and GFP with the methylester forms of N-epsilon-Boc-L-Lysine (BocK) and N-epsilon-propargyl-L-Lysine (PrK) by 2-5 folds compared to their free acid forms. Our work demonstrated that using methylester-capped UAAs for protein expression is a useful strategy to enhance the yields of UAA-incorporated proteins.

【 授权许可】

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