Electrospray tandem mass spectrometry of alkali‐cationized BocN‐carbo‐α,β‐ and ‐β,α‐peptides: differentiation of positional isomers

Abstract

Dissociation pathways of a series of alkali-cationized hybrid peptides, viz., Boc-alpha,beta- and -beta,alpha-carbopeptides, synthesized from C-linked carbo-beta3-amino acids [Caa (S)] and alpha-alanine (L-Ala), have been investigated by electrospray ionization tandem mass spectrometry. The positional isomers (six pairs) of the cationized alpha,beta- and beta,alpha-peptides can be differentiated by the collision-induced dissociation (CID) spectra of their [M + Cat-Boc + H]+ ions which give characteristic series of alkali-cationized C- (x(n)+, y(n)+, z(n)+) and N-terminal (a(n)+, b(n)+, c(n)+) ions. Another noteworthy difference is cationized beta,alpha-peptides eliminate a molecule of ammonia whereas this pathway is absent for alpha,beta-peptides. This is useful for identifying the presence of a beta-amino acid at the N-terminus. The CID spectra of [M + Cat-Boc + H]+ ions of these peptide acids show abundant rearrangement [b(n) + 17 + Cat]+ (n = 1 to n-1) ions which is diagnostic for distinguishing between alpha- and beta-amino acid at the C-terminus. MS(n) experiments of [b(n) + Li-H]+ ions from these hybrid peptides showed the loss of CO and 72 u giving rise to [a(n) + Li-H]+ and cationized nitrile product ions which render support to earlier proposals that b(n)+ or [b(n) + Cat-H]+ ions have protonated or cationized oxazolinone structures, respectively.

Diastereomeric differentiation of norbornene amino acid peptides by electrospray ionization tandem mass spectrometry

“…Mass spectral characterization of α ‐amino acid peptides is well documented in the literature7–9 and the tandem mass spectrometry (MS/MS) of protonated peptides formed in fast atom bombardment (FAB), electrospray ionization (ESI),10–15 and matrix‐assisted laser desorption/ionization (MALDI)16–18 mass spectrometry (MS) is an established tool in determining amino acid sequence of peptides. There are very few reports available in the literature on the mass spectral study of peptides derived from nonnatural amino acids, which are important from the view point of foldamer chemistry and pharmaceutical chemistry as described above 19–29. Because of this, it is desirable to study the structural characterization including the stereochemical differentiation of this class of peptides by mass spectrometric techniques.…”

“…Because of this, it is desirable to study the structural characterization including the stereochemical differentiation of this class of peptides by mass spectrometric techniques. We have reported earlier MS/MS of hybrid carbopeptides20–29 and differentiated positional and diastereomeric isomers of some of these peptides 20–27. Recently, we reported a study on the effect of N‐terminal β ‐ and γ ‐carboamino acids on fragmentation of γ ‐aminobutyric acid (GABA‐)containing hybrid peptides 28.…”

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].…”