Bioconjugation Chemistry: Challenges and Solutions

Bioconjugation represents the derivatization of biomolecules (proteins, carbohydrates, nucleic acids) which allows the site-specific creation of a covalent link between a biomolecule and an exogenous moiety in order to endow desirable properties using a different set of techniques.^1,2 Bioconjugation biochemistry enables the creation of hybrid molecules that exhibit the properties of both biomolecules and exogenous moieties. Examples of bioconjugation based hybrid molecules include protein structure elucidation using tags, enzyme immobilization, antibodies binding to fluorophores, cellular imaging, microarrays, etc.^3,4. Bioconjugation typically involves the modification of biomolecules by adding distinct but complementary functional groups through a wide range of chemical techniques/reactions using different linkers. However, to develop new methodologies, site specific conjugation continues to garner much attention to match the ever-increasing requirements of preserving biomolecule integrity, stability, and mildness. Nevertheless, bioconjugation techniques have emerged as a powerful set of tools with applications in ground-breaking targeted biotherapeutics, disease diagnosis, ligand discovery, high throughput drug screening, biosensors.^5,6,7