Photocrosslinking and capture for the analysis of carbohydrate-dependent interactions

Carbohydrates play crucial roles in biological systems, including by mediating cell and protein interactions. The complexity and transient nature of carbohydrate-dependent interactions pose significant challenges for their characterization, as traditional techniques often fail to capture these low-affinity binding events. This review highlights the increasing utility of photocrosslinkers in studying carbohydrate-mediated interactions. Photocrosslinkers, such as aryl azides, benzophenones, and diazirines, allow for the capture of fleeting interactions by forming covalent bonds upon UV irradiation, enabling the downstream application of standard biochemical techniques. I discuss the three primary strategies for incorporating photocrosslinkers: synthetic small molecules, metabolic labeling, and exo-enzymatic labeling. I predict that the continued development and application of these methodologies will enhance our understanding of glycan-mediated interactions and their implications in health and disease.