Mapping Peptide-Protein Interactions by Amine-Reactive Cleavable Photoaffinity Reagents.

ABSTRACT: Photoaffinity labeling followed by tandem mass spectrometry is an often used strategy to identify protein targets of small-molecule drugs or drug candidates, which, under ideal conditions, enables the identification of the actual drug binding site. In the case of bioactive peptides, however, identifying the distinct binding site is hampered because of complex fragmentation patterns during tandem mass spectrometry. We here report the development and use of small cleavable photoaffinity reagents that allow functionalization of bioactive peptides for light-induced covalent binding to their protein targets. Upon cleavage of the covalently linked peptide drug, a chemical remnant of a defined mass remains on the bound amino acid, which is then used to unambiguously identify the drug binding site

SUBMITTER: Korovesis D 

PROVIDER: S-EPMC10357517 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature