Host-guest chemistry in the gas phase: selected fragmentations of CB[6]-peptide complexes at lysine residues and its utility to probe the structures of small proteins

The gas phase host-guest chemistry between cucurbit6]uril (CB6]) and peptide is investigated using electrospray ionization mass spectrometry (ESI-MS). CB6] exhibits a high preference to interacting with a Lys residue in a peptide forming a CB6]-peptide complex. Collisionally activated CB6] complexes of peptides yield a common highly selective fragment product at m/z 549.2, corresponding to the doubly charged CB6] complex of 5-iminiopentylammonium (5IPA). The process involves the formation of an internal iminium ion, which results from further fragments to an a-type ion from a y-type ion, and the resulting 5IPA ion threads through CB6]. Numerous peptides are investigated to test the generality of the observed unique host-guest chemistry of CB6]. Its potential utility in probing protein structures is demonstrated using CB6] complexes of ubiquitin. Low-energy collision induced dissociation yields CB6] complex fragments, and further MS(n) spectra reveal details of the CB6] binding sites, which allow us to deduce the protein structure in the solution phase. The mechanisms and energetics of the observed reactions are evaluated using density functional theory calculations.