Stereospecific control of peptide gas-phase ion chemistry with cis and trans cyclo ornithine residues

Abstract

We report non-chiral amino acid residues cis- and trans-1,4-diaminocyclohexane-1-carboxylic acid (cyclo-ornithine, cO) that exhibit unprecedented stereospecific control of backbone dissociations of singly charged peptide cations and hydrogen-rich cation radicals produced by electron-transfer dissociation. Upon collision-induced dissociation (CID) in the slow heating regime, peptide cations containing trans-cO residues undergo facile backbone cleavages of amide bonds C-terminal to trans-cO. By contrast, peptides with cis-cO residues undergo dissociations at several amide bonds along the peptide ion backbone. Diastereoisomeric cO-containing peptides thus provide remarkably distinct tandem mass spectra. The stereospecific effect in CID of the trans-cO residue is explained by syn-facially directed proton transfer from the 4-ammonium group at cO to the C-terminal amide followed by neighboring group participation in the cleavage of the CO-NH bond, analogous to the aspartic acid and ornithine effects. Backbone dissociations of diastereoisomeric cO-containing peptide ions generate distinct [b_n ]⁺ -type fragment ions that were characterized by CID-MS³ spectra. Stereospecific control is also reported for electron-transfer dissociation of cis- and trans-cO containing doubly charged peptide ions. The stereospecific effect upon electron transfer is related to the different conformations of doubly charged peptide ions that affect the electron attachment sites and ensuing N-C_α bond dissociations.

Keywords: cis and trans isomers; cyclo ornithine; peptide dissociations; peptide ion structures; stereochemistry.