Differentiation of three pairs of positional isomers of hybrid peptides with repeats of phenylalanine‐β³‐h‐valine/β³‐h‐valine‐phenylalanine by electrospray ionization tandem mass spectrometry

Abstract

Electrospray ionization ion trap mass spectrometry has been used to distinguish three pairs of positional isomers of a new series of N-blocked hybrid peptides derived from repeats of phenylalanine(D)-beta3-h-valine/beta3-h-valine-phenylalanine(D) (FbetaV/betaVF) non-natural amino acids. MSn of protonated isomeric peptides produces characteristic fragmentation involving the peptide backbone, the Boc group and the side chain. FbetaV-peptides can be distinguished from betaVF-peptides by the loss of R-OH from [M+H-Boc+H]+, which is either of relatively low abundance or totally absent for the latter peptides. In contrast, betaVF-peptides show abundant Mannich base characteristic ions by the elimination of ammonia, and imine due to a retro-Mannich cleavage. This fragmentation is absent for FbetaV-peptides. When beta-valine is at the C-terminus, abundant b+(n-1) ions are produced. This is ascribed to the probable formation of a stable diketopiperazine structure, and this has been supported by the loss of H2O and CO in the CID spectra of b+(n-1) ions. The hybrid dipeptide acids have also been distinguished in negative ion mass spectrometry.

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

“…ESI ion-trap mass spectra of di-and tetrapeptides (Scheme 1) were recorded using an Liquid Chromatography Quadrupole (LCQ) ion-trap mass spectrometer 38 (Thermo Finnigan, San Jose, CA, USA), equipped with an ESI source. The data acquisition was under the control of Xcalibur software (Thermo Finnigan).…”

Electrospray ionization-ion trap mass spectrometry study of PQAAPro and PQProAA mimetic derivatives of the antimalarial primaquine

“…Overall, this work embodies an original and valuable contribution towards a deeper insight into the molecular properties of novel antimalarials, which can be viewed as representative of both the O ver the past decade, electrospray ionization mass spectrometry (ESI-MS) has been used for the most diverse analytical purposes. This technique has provided deeper insight into the structural properties and stability of numerous compounds, from natural products [1][2][3] to synthetic drugs [4][5][6][7][8], peptides [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23], and heterocycles [24][25][26][27][28], among many others. Notwithstanding, little has been done on the application of this technique to the study of relevant antimalarials such as primaquine (PQ, 1) or related structures.…”

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

“…The CID spectra of both the diastereomers display the abundant Boc characteristic ion, [M+H–Boc+H] + ( m/z 168), and other common ions at m/z 180 (loss of methyl tert ‐butyl ether), m/z 151 [M+H–Boc+H–NH 3 ] + , m/z 136 [M+H–Boc+H–CH 3 OH] + and m/z 91 [C 7 H 7 ] + . The formation of [M+H–Boc+H] + can be rationalized in terms of a McLafferty‐type rearrangement involving a γ ‐hydrogen migration from one of the methyl groups of the tert ‐butyl group to the carbonyl oxygen in the Boc‐N moiety followed by the loss of C 4 H 8 and subsequent loss of CO 2 20–29. The ion at m/z 180 may be formed due to an ortho interaction between the ‐NH‐Boc and the carbomethoxy group.…”

“…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.…”