Genetic Encoding of a Bioconjugation Handle for [2+2+2] Cycloaddition Reactions. (17th October 2019)

• Record Type: Journal Article
• Authors: Travis, Christopher R.; King, Elizabeth A.; Gaunt, Gillian H.; Young, Douglas D.
• Is Part Of: Chembiochem. Volume 21:Number 3(2020)
• Page Start: 310
• Page End: 314
• Publication Date: 2019-10-17
• Subjects: alkynes -- bioconjugation -- cycloaddition -- unnatural amino acids; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201900391
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Protein bioconjugates have many critical applications, especially in the development of therapeutics. Consequently, the design of novel methodologies to prepare protein bioconjugates is of great importance. Herein we present the development and optimization of a novel strategy to prepare bioconjugates through a genetically encoded [2+2+2] cycloaddition reaction. To do this, a novel unnatural amino acid (UAA) containing a dipropargyl amine functionality was synthesized and incorporated site specifically. This UAA‐containing protein was reacted with an alkyne‐containing fluorophore to afford a covalently linked, well‐defined protein bioconjugate. This reaction is convenient with an optimized reaction time of just two hours at room temperature and yields a stable, polysubstituted benzene ring. Overall, this work contributes a new bioconjugation strategy to the growing toolbox of reactions to develop protein bioconjugates, which have a myriad of applications. Abstract : A new unnatural amino acid has been synthesized and genetically encoded into a protein. This functionality facilitated the development of a novel [2+2+2] cycloaddition bioconjugation, as well as its use in previously developed conjugation reactions.