Investigation of peptide microsolvation in the gas phase by radical directed dissociation mass spectrometry

•Radical Directed Dissociation (RDD) is a sensitive technique suitable for probing peptide structure.•18-Crown-6 attachment influences peptide structure in the gas phase.•Long peptides with basic side chains are influenced most by 18-crown-6 complexation.

Peptide structure is often correlated with biological function, and recently interest in developing gas-phase based methods for examining peptide structure has grown. The relationship between solution and gas phase structures is unclear, partially due to removal of solvent during the transition. 18-Crown-6 (18C6) is a small molecule that can noncovalently attach to peptides in the gas phase via basic residues, perhaps replacing water and helping retain solution-like structures. Herein, we investigate structural differences between naked peptides and those solvated by 18C6 with radical directed dissociation (RDD), a structurally sensitive fragmentation method. Peptides with and without 18C6 attached often yield disparate RDD spectra, indicating significant structural differences between them. The effects of solvation by 18C6 were explored as a function of peptide size and sequence. Although general trends can be observed with regard to factors that influence solvation, the results suggest that solvation is unique for each peptide and should be examined on a case by case basis.

Graphical abstractDownload high-res image (84KB)Download full-size image