Bioconjugation

Bioconjugation is a chemical strategy to form a stable covalent link between two molecules, at least one of which is a biomolecule. Recent advances in the understanding of biomolecules enabled their application to numerous fields like medicine and materials. Synthetically modified biomolecules can have diverse functionalities, such as tracking cellular events, revealing enzyme function, determining protein biodistribution, imaging specific biomarkers, and delivering drugs to targeted cells. Bioconjugation is a crucial strategy that links these modified biomolecules with different substrates. Besides applications in biomedical research, bioconjugation has recently also gained importance in nanotechnology such as bioconjugated quantum dots. The most common types of bioconjugation include coupling of a small molecule (such as biotin or a fluorescent dye) to a protein. Antibody-drug conjugates such as Brentuximab vedotin and Gemtuzumab ozogamicin are examples falling into this category. Protein-protein conjugations, such as the coupling of an antibody to an enzyme, is also common in bioconjugations. Other less common molecules used in bioconjugation are oligosaccharides, nucleic acids, synthetic polymers such as polyethylene glycol, and carbon nanotubes. Synthesis of bioconjugates involves a variety of challenges, ranging from the simple and nonspecific use of a fluorescent dye marker to the complex design of antibody drug conjugates. Various bioconjugation reactions have been developed to chemically modify proteins. Common types of bioconjugation reactions on proteins are coupling of lysine, cysteine, and tyrosine amino acid residues, as well as modification of tryptophan residues and of the N- and C- terminus. However, these reactions often lack chemoselectivity and efficiency, because they depend on the presence of native amino acids, which are present in large quantities that hinder selectivity. There is an increasing need for chemical strategies that can effectively attach synthetic molecules site specifically to proteins.