Expanding the Scope of Bioconjugations Using Non-Canonical Amino Acids

Protein bioconjugates, or proteins that are covalently bound to other molecules, have applications in a wide variety of fields including drug delivery, diagnostic imaging, and materials. For many of these applications, bioconjugation techniques that afford site-specific, homogenous conjugates are desirable. The incorporation of non-canonical amino acids (ncAAs) into proteins can provide bioorthogonal reaction handles that can be exploited in the synthesis of such conjugates. To this end, this thesis seeks to exploit ncAAs in the development of novel reactions and/or reaction sequences to couple proteins to one or more reaction partners in a site-specific manner. The development of a novel reaction cascade that employs a single bromoalkyne ncAA in the synthesis of a site-specific multivalent conjugate is explored. Novel hydroamination and hydrochalcogenation bioconjugation reactions that exploit a variety of alkynyl functionalities to generate divalent and multivalent conjugates are also investigated.