Covalent crosslinking in gas-phase biomolecular ions. An account and perspective

Abstract

Photochemical crosslinking in gas-phase ion complexes has been introduced as a method to study biomolecular structures and dynamics. Emphasis has been on carbene-based crosslinking induced by photodissociation of diazirine-tagged ions. The features that characterize gas-phase crosslinking include (1) complex formation in electrospray droplets that allows for library-type screening; (2) well defined stoichiometry of the complexes due to mass-selective isolation; (3) facile reaction monitoring and yield determination, and (4) post-crosslinking structure analysis by tandem mass spectrometry that has been combined with hydrogen–deuterium exchange, UV-vis action spectroscopy, and ion mobility measurements. In this account, examples are given of peptide–peptide, peptide–nucleotide, and peptide–ligand crosslinking that chiefly used carbene-based reactions. The pros and cons of gas-phase crosslinking are discussed. Nitrile-imine based crosslinking in gas-phase ions is introduced as a promising new approach to ion structure analysis that offers high efficiency and has the potential for wide ranging applications.