Bioconjugation of therapeutic proteins and enzymes using the expanded set of genetically encoded amino acids

Abstract

The last decade has witnessed striking progress in the development of bioorthogonal reactions that are strictly directed towards intended sites in biomolecules while avoiding interference by a number of physical and chemical factors in biological environment. Efforts to exploit bioorthogonal reactions in protein conjugation have led to the evolution of protein translational machineries and the expansion of genetic codes that systematically incorporate a range of non-natural amino acids containing bioorthogonal groups into recombinant proteins in a site-specific manner. Chemoselective conjugation of proteins has begun to find valuable applications to previously inaccessible problems. In this review, we describe bioorthogonal reactions useful for protein conjugation, and biosynthetic methods that produce proteins amenable to those reactions through an expanded genetic code. We then provide key examples in which novel protein conjugates, generated by the genetic incorporation of a non-natural amino acid and the chemoselective reactions, address unmet needs in protein therapeutics and enzyme engineering.

• Bioorthogonal chemistry
• drug delivery
• immobilization
• monoclonal antibody
• non-natural amino acid
• protein chemistry
• protein conjugation
• site-specific incorporation

Declaration of interest

The work was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (grant 2014R1A2A1A11050322). and the Bio Imaging Research Center at GIST. The authors report no declarations of interest.

Supplementary material available online.

Supplementary Table S1 and Figure S1.