Positive and negative ion electrospray tandem mass spectrometry (ESI MS/MS) of boc-protected peptides containing repeats of L-Ala-γ⁴Caa/γ⁴Caa-L-Ala: Differentiation of some positional isomeric peptides

Abstract

High-resolution electrospray ionization (ESI) quadrupole time-of-flight and ion trap tandem mass spectrometry has been used to distinguish the positional isomers of a new class of N-blocked hybrid peptides containing repeats of the amino acids, L-Ala-gamma(4)Caa ((l))/gamma(4)Caa((l))-L-Ala [Caa((l)) = Carbo (lyxose) amino acid, derived from D-mannose]. Both MS/MS and MS(3) of protonated isomeric peptides produce characteristic fragmentation involving the peptide backbone, Boc-group, and the side-chain. It is interesting to observe that the abundant y(n)(+) ions are formed when the corresponding amide -NH does not participate in the helical structures in solution phase and relatively low abundance y(n)(+) ions resulted when the amide -NH involves in the H-bonding. Thus, it was possible to identify the amide -NH hydrogens that participate in the helical structures through H-bonding in solution phase. Further, negative ion ESI MS/MS has also been found to be useful for differentiating these isomeric peptide acids.

Differentiation of three pairs of Boc‐β,γ‐ and γ,β‐hybrid peptides by electrospray ionization tandem mass spectrometry

“…All the samples were infused into the ESI source at a flow rate of 5 µl/min by using the instrument's syringe pump. ESI mass spectra for hexapeptides (Scheme 1) were recorded using a quadrupole time-of-flight (Q-TOF) mass spectrometer 37 (QSTAR XL, Applied Biosystems/MDS Sciex, Foster City, USA), equipped with an ESI source. The data acquisition was under the control of Analyst QS software (Foster City, CA).…”

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)

“…The negative ion ESI of di-(11-16) tetra-(17-18) and hexa -ions [39,41,[43][44][45][46]54]. The formation of these ions may presumably be due to a 1,3-H migration from -NH-to the ‛ O of the butyloxy group leading to the elimination of tert-butanol by charge-remote fragmentation [46].…”

“…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].…”

“…We have studied the differentiation of four pairs of diastereomers of norbornene amino acid peptides using electrospray ionization tandem mass spectrometry [48]. We have also shown that MS/MS of some of the α,γ-/γ,α-peptides can be used to identify the -NH-hydrogens that participate in the hydrogen bonding leading to helical structure in solution phase [44].…”