Selective Functionalization of Peptides with Reactive Fragment Ions

Selective binding of highly reactive inorganic fragment ions generated in a mass spectrometer to peptides within surface layers is demonstrated using the sequential mass-selected deposition of the reagents. The closo-dodecaborate fragment ions [B₁₂I₁₁]^- and [B₁₂I₈S(CN)]^- were generated by collision-induced dissociation and bound to three dipeptides: leucyl proline, phenylalanyl proline, and tyrosyl proline. The products formed on the deposition surface were structurally characterized by electrospray ionization tandem mass spectrometry. Deuterium labeling was employed to investigate the reaction. The fragment ion [B₁₂I₁₁]^- is demonstrated to react via "first contact" with the vacuum-oriented hydrophobic N-terminal side chains of the peptides, forming selectively nonthermochemically preferred isomers. In contrast, the less reactive fragment ion [B₁₂I₈S(CN)]^- reacts with the polar functional groups of the peptides, forming mainly thermochemically preferred products. The results demonstrate selectivity control in the formation of bioconjugates by using reactive, unconventional chemical "building blocks" from the gas phase.