Visible-Light-Mediated Modification and Manipulation of Biomacromolecules

Abstract

Chemically modified biomacromolecules─i.e., proteins, nucleic acids, glycans, and lipids─have become crucial tools in chemical biology. They are extensively used not only to elucidate cellular processes but also in industrial applications, particularly in the context of biopharmaceuticals. In order to enable maximum scope for optimization, it is pivotal to have a diverse array of biomacromolecule modification methods at one's disposal. Chemistry has driven many significant advances in this area, and especially recently, numerous novel visible-light-induced photochemical approaches have emerged. In these reactions, light serves as an external source of energy, enabling access to highly reactive intermediates under exceedingly mild conditions and with exquisite spatiotemporal control. While UV-induced transformations on biomacromolecules date back decades, visible light has the unmistakable advantage of being considerably more biocompatible, and a spectrum of visible-light-driven methods is now available, chiefly for proteins and nucleic acids. This review will discuss modifications of native functional groups (FGs), including functionalization, labeling, and cross-linking techniques as well as the utility of oxidative degradation mediated by photochemically generated reactive oxygen species. Furthermore, transformations at non-native, bioorthogonal FGs on biomacromolecules will be addressed, including photoclick chemistry and DNA-encoded library synthesis as well as methods that allow manipulation of the activity of a biomacromolecule.