A bifunctional amino acid to study protein-protein interactions

Protein-protein interactions (PPIs) play crucial roles in regulating essentially all cellular processes. Photo-cross-linking represents a powerful method to study PPIs. To fulfil the requirements for the exploration of different PPIs, there is a continuous demand on the development of novel photo-reactive amino acids with diverse structural properties and functionalities. Reported herein is the development of a bifunctional amino acid termed dzANA , which contains a diazirine, for photo-cross-linking, and a terminal alkyne group, for bioorthogonal tagging. Using known PPIs between histone posttranslational modifications (PTMs) and their binding partners as models, we demonstrate that the dzANA -harbouring peptide-based photoaffinity probes could efficiently and selectively capture the weak and transient PPIs mediated by histone modifications. Our study indicates the potential of dzANA to identify and characterize unknown PPIs. dzANA is a novel bifunctional (photo-reactive and bioorthogonal) amino acid to study protein-protein interactions.