title: 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.
authors.affiliation: a Department of Chemical Engineering , University of Virginia , Charlottesville , VA , USA and.
authors.forename: Sung In
authors.initials: SI
authors.lastname: Lim
authors.affiliation: a Department of Chemical Engineering , University of Virginia , Charlottesville , VA , USA and.|b School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST) , Gwangju , Republic of Korea.
authors.forename: Inchan
authors.initials: I
authors.lastname: Kwon
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000235:genetics; D000818:Animals; D005815:Genetic Code; D006801:Humans; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*
chemical_list: D000596:Amino Acids; D011506:Proteins
keywords: Bioorthogonal chemistry; drug delivery; immobilization; monoclonal antibody; non-natural amino acid; protein chemistry; protein conjugation; site-specific incorporation