Comparative Analysis of the Reactivity of Diazirine‐Based Photoaffinity Probes toward a Carbohydrate‐Binding Protein

A set of lactose‐based photoaffinity probes bearing either alkyl diazirine or trifluoromethylphenyl diazirine (TPD) groups were designed and synthesized to directly compare their efficiency in photocrosslinking a carbohydrate‐binding protein. The crosslinking efficiency of the TPD probes was higher than the alkyl diazirine probes when reacted with a single binding protein. However, the alkyl diazirine probe with a small alkyne tag achieved more selective photoaffinity labeling of a binding protein in cell lysate than the corresponding TPD probe.