Mass spectral study of alkali‐cationized Boc‐carbo‐β³‐peptides by electrospray tandem mass spectrometry

Abstract

Electrospray tandem mass spectrometry was used to study the dissociation reactions of [M+Cat]+ (Cat = Na+ and Li+) of Boc-carbo-beta3-peptides. The collision-induced dissociation (CID) spectra of [M+Cat-Boc]+ of these peptides are found to be significantly different from those of [M+H-Boc]+ ions. The spectra are more informative and display both C- and N-terminus metallated ions in addition to characteristic fragment ions of the carbohydrate moiety. Based on the fragmentations observed in the CID spectra of the [M+Cat-Boc]+ ions, it is suggested that the dissociation involves complexes in which the metal ion is coordinated in a multidentate arrangement involving the carbonyl oxygen atoms. The CID spectra of [M+Cat-Boc]+ ions of the peptide acids show an abundant N-terminal rearrangement ion [b(n)+17+Cat]+ which is absent for esters. Further, two pairs of positionally isomeric Boc-carbo-beta3-peptide acids, Boc-NH-Caa(S)-beta-hGly-OH (11) and Boc-NH-beta-hGly-Caa(S)-OH (12), and [Boc-NH-Caa(S)-beta-hGly-Caa(S)-beta-hGly-OH] (13) and [Boc-NH-beta-hGly-Caa(S)-beta-hGly-Caa(S)-OH] (14), were differentiated by the CID of [M+Cat-Boc]+ ions. The CID spectra of compounds 11 and 13 are significantly different from those of 12 and 14, respectively. The abundance of [b(n)+17+Cat]+ ions is higher for peptide acids 12 and 14 with a sugar group at the C-terminus when compared to 11 and 13 which contain a sugar moiety at the N-terminus. The observed differences between the CID spectra of these isomeric peptides are attributed to the difference in the preferential site of metal ion binding and also on the structure of the cyclic intermediate involved in the formation of the rearrangement ion.

Differentiation of Positional Isomers of Hybrid Peptides Containing Repeats of β-Nucleoside Derived Amino Acid (β-Nda-) and L-Amino Acids by Positive and Negative Ion Electrospray Ionization Tandem Mass Spectrometry (ESI-MSn)

“…Formation of this ion can be explained by a 'H' migration from the active β-methylene group to the -NCO [40,42,45,46] -ions of all these isomeric peptides display an abundant m/z 125 ion corresponding to thymine anion [58,59].…”

“…The tandem mass spectrometry (MS/MS) of protonated [21][22][23][24][25][26][27], deprotonated peptides [28][29][30][31][32][33] in electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) [34][35][36][37] have been used for structure elucidation of peptides. There are very few reports in the literature on the mass spectral study of peptides derived from non-natural amino acids [38][39][40][41][42][43][44][45][46][47][48]. We have reported ESI-MS/MS of a series of Boc-protected carbopeptides [39][40][41][42][43][44][45][46][47][48], and differentiated both positional and diastereomeric isomers [39][40][41][42][43][44][45][46]48].…”

“…There are very few reports in the literature on the mass spectral study of peptides derived from non-natural amino acids [38][39][40][41][42][43][44][45][46][47][48]. We have reported ESI-MS/MS of a series of Boc-protected carbopeptides [39][40][41][42][43][44][45][46][47][48], and differentiated both positional and diastereomeric isomers [39][40][41][42][43][44][45][46]48]. Recently, we have reported a study on the effect of Nterminal β-and γ-carbo amino acids on the fragmentation of γ-amino butyric acid (γ-Abu) containing hybrid peptides [46].…”

Differentiation of α- or β-Aspartic Isomers in the Heptapeptides by the Fragments of [M + Na]+Using Ion Trap Tandem Mass Spectrometry

“…The presence of a fixed positive charge or a sodium ion in the peptide promoted this selective reaction [31][32][33]. Various mechanisms had been proposed to explain the formation of product ions formed via CID of [M+Na] + of peptides [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. For example, a sodium ion associated with the C-terminal carboxylic group has been proposed to initiate a rearrangement reaction of hydroxyl group leading to sequential loss of the C-terminal amino acid during multiple stages of MS/MS process [34][35][36].…”

In‐source decay of Boc‐carbo‐β3‐peptides in matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry

“…Surprisingly, the spectra do not exhibit any metallated sequence ions, which is in contrast with the behavior of these peptides under LSI and ESI conditions. 29 However, low-abundance free y n þ and b n þ ions are observed in the cases of tetra-to hexa-peptides. (Fig.…”