Light-induced chemistry for protein functionalisation

Derivatising biomolecules like monoclonal antibodies with drugs or imaging agents, whilst preserving their bioactivity, is a challenging task. Protein functionalisation ideally requires methods that operate under mild conditions, are rapid, efficient (high yielding), chemoselective or site-specific, and importantly, non-denaturing. A broad collection of thermally mediated reagents for direct labelling using protein-based reactivity, or bioorthogonal strategies, has been developed, but arguably the most exciting opportunities lie in the application of photochemistry to create new covalent bioconjugate bonds. With current chemical methods for auxochromic tuning of the spectral features of photoactive groups, and with cheap, high-powered light-emitting diodes with precise emission properties, it has never been easier to explore the use of light-induced chemistry for making protein-based bioactive molecules. In biomedicine, the nature of the covalent bond to the protein can have a dramatic impact on the physicochemical properties and performance of the protein-conjugate. Photochemical methods provide access to new types of covalent linkages on protein with the potential to fine-tune biological interactions, leading to improvements in target uptake, binding specificity, metabolic processing, and washout kinetics in vivo. This perspective/review highlights recent advances in the development of photoactive reagents for protein labelling. We also discuss the experimental conditions and critical requirements to implement light-induced synthesis of functionalised protein-conjugates in aqueous media effectively.