Non‐covalent interactions of alkali metal cations with singly charged tryptic peptides

Abstract

The complexes formed by alkali metal cations (Cat + = Li + ,Na + ,K + ,Rb + ) and singly charged tryptic peptides were investigated by combining results from the low-energy collision-induced dissociation (CID) and ion mobility experiments with molecular dynamics and density functional theory calculations. The structure and reactivity of [M+H +Cat] 2+ tryptic peptides is greatly influenced by charge repulsion as well as the ability of the peptide to solvate charge points. Charge separation between fragment ions occurs upon dissociation, i.e. b ions tend to be alkali metal cationised while y ions are protonated, suggesting the location of the cation towards the peptide N-terminus. The low-energy dissociation channels were found to be strongly dependant on the cation size. Complexes containing smaller cations (Li + or Na + ) dissociate predominantly by sequence-specific cleavages, whereas the main process for complexes containing larger cations (Rb + ) is cation expulsion and formation of [M + H] + . The obtained structural data might suggest a relationship between the peptide primary structure and the nature of the cation coordination shell. Peptides with a significant number of side chain carbonyl oxygens provide good charge solvation without the need for involving peptide bond carbonyl groups and thus forming a tight globular structure. However, due to the lack of the conformational flexibility which would allow effective solvation of both charges (the cation and the proton) peptides with seven or less amino acids are unable to form sufficiently abundant [M+H+Cat] 2+ ion. Finally, the fact that [M+H+Cat] 2+ peptides dissociate similarly as [M + H] + (via sequence-specific cleavages, however, with the additional formation of alkali metal cationised b ions) offers a way for generating the low-energy CID spectra of 'singly charged' tryptic peptides.

Study of the gas-phase fragmentation behaviour of sulfonated peptides

“…Combination of quenched dynamics and simulated annealing with the AMBER 99 force field was used to sample the potential energy surface of the test peptides (TSQLL and SAALSLLR) by the protocol identical to that previously used [7,22]. Final structures were reoptimised using the B3LYP/6-31G(d) level of theory and the lowest energy structure was considered as the representative structure.…”

Gas Phase Chemistry of Li+with Amides: the Observation of LiOH Loss in Mass Spectrometry

“…The CID mass spectrum of the lithiated deuterated Compound 1 is shown as Figure 1b. Upon collisional activation after H/D exchange, interestingly, the ions at m/z 350 and 351 were both observed, and the formulas were confirmed to be C 19 (Table S2). The existence of ion at m/z 351, which results from the loss of LiOH, implies that the deuteron migrates to the phenyl ring and exchanges with the proton on the phenyl ring.…”

“…On the other hand, the mass spectrometric fragmentations of metal cationized, especially lithiated biomolecules, have attracted much attention because of the desire to measure intrinsic metal ion affinity and identify the binding sites [14,15], and because the interesting dissociation pathways exhibited by these compounds are usually different from the protonated and deprotonated analogues [16,17]. Recently, the fragmentation behaviors of lithiated species have been reported for peptides, fatty acids, phospholipids, polytetrahydrofuran, cardiolipins, thioesters, cholesteryl esters, and disaccharides [18][19][20][21][22][23][24][25][26].…”

Self‐Assembled Multimetallic/Peptide Complexes: Structures and Unimolecular Reactions of [Mn(GlyGly−H)2n−1]+ and Mn+1(GlyGly−H2n]2+ Clusters in the Gas Phase

“…Collision-induced dissociation (CID) is aw idely used method for structure elucidationo fc omplexes of metal cations with biomolecules such as amino acids, [23][24][25][26][27][28][29] peptides, [30][31][32] and nucleic acid bases. [33,34] The effecto fm etal cations on the dissociation pattern and activation energy of amino acid complexes have been studied by CID.…”