Advancing protein engineering via organic chemistry

Proteins are central to nearly all biological processes; their functions are tightly regulated by dynamic mechanisms such as covalent alterations; e.g., post-translational modifications (PTMs). These modifications can influence the protein’s structure, localization, and activity. Inspired by this diversity and regulation, advances in synthetic organic chemistry have enabled the production of a plethora of novel proteins for both basic research and biomedical applications. Recent progress in structural elucidation technologies and modern organic chemistry has enabled atom-level modifications, significantly enhancing our ability to tailor protein function. These approaches greatly expand the toolkit currently available for generating complex proteins with unique structural and functional properties. In this review, we summarize recent progress in chemical protein engineering and highlight its emerging applications in catalysis, functional studies, and drug development. Selective protein functionalization remains difficult to achieve through conventional molecular biology approaches. Here, the authors summarize recent advances in chemical approaches to protein engineering and highlight their emerging applications in catalysis, functional studies, and therapeutic development.