Ion spectroscopy and guided ion beam studies of protonated asparaginyl-threonine decomposition: Influence of a hydroxyl containing C-Terminal residue on deamidation processes

Boles, Georgia C.; Kempkes, Lisanne J. M.; Martens, Jonathan; Berden, Giel; Armentrout, P. B.

doi:10.1016/j.ijms.2019.05.010

Cited by 7 publications

(45 citation statements)

References 54 publications

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“…If dehydration follows a parallel mechanism, expelling H 2 O from the Asn side-chain with the backbone amide nitrogen acting as the nucleophile, a pyrrolidone ring-containing product would be formed (structure 5 in Scheme 3 ). For protonated AsnThr, however, the [AsnThr + H – H 2 O] + spectrum reported in ref ( 53 ) indicates that an oxazoline structure is formed, consistent with the other [XxxThr + H – H 2 O] + systems presented here. Below, we investigate the dehydration of protonated AsnSer.…”

Section: Resultssupporting

confidence: 90%

“…In contrast to the XxxSer and XxxThr peptides discussed above, AsnSer and AsnThr contain additional nucleophiles that may influence the dehydration reaction and the resulting product ion structure. Deamidation of these peptides was shown to expel NH 3 from the amide moiety in the Asn side-chain, forming a furanone ring product ion, 53 which is rationalized by ring closure between the Asn amide carbon atom and the backbone amide nitrogen. If dehydration follows a parallel mechanism, expelling H 2 O from the Asn side-chain with the backbone amide nitrogen acting as the nucleophile, a pyrrolidone ring-containing product would be formed (structure 5 in Scheme 3 ).…”

Section: Resultsmentioning

confidence: 99%

“… 43 , 51 − 53 Very recently, we used ion spectroscopy to investigate deamidation and dehydration of protonated AsnThr, which suggested that water loss indeed does not occur from the C-terminus, leading to a product ion containing an oxazoline—not oxazolone—moiety ( Schemes 1 and 2 ). 53 Computational investigations of the potential energy surface (PES) suggested the participation of the Asn side-chain amide moiety so that the question of whether the formation of an oxazoline fragment is a generic pathway for Thr- and Ser-containing peptides is relevant. Therefore, we address here dipeptides with an aliphatic side-chain at the first residue (AlaSer, AlaThr, GlySer, GlyThr, PheSer, PheThr, ProSer, and ProThr) and compare with results for AsnSer and AsnThr.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, we address here dipeptides with an aliphatic side-chain at the first residue (AlaSer, AlaThr, GlySer, GlyThr, PheSer, PheThr, ProSer, and ProThr) and compare with results for AsnSer and AsnThr. 53 …”

Section: Introductionmentioning

confidence: 99%

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Water Loss from Protonated XxxSer and XxxThr Dipeptides Gives Oxazoline—Not Oxazolone—Product Ions

Kempkes

Geurts

Dijk

et al. 2020

J. Am. Soc. Mass Spectrom.

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Neutral loss of water and ammonia are often significant fragmentation channels upon collisional activation of protonated peptides. Here, we deploy infrared ion spectroscopy to investigate the dehydration reactions of protonated AlaSer, AlaThr, GlySer, GlyThr, PheSer, PheThr, ProSer, ProThr, AsnSer, and AsnThr, focusing on the question of the structure of the resulting [M + H – H 2 O] + fragment ion and the site from which H 2 O is expelled. In all cases, the second residue of the selected peptides contains a hydroxyl moiety, so that H 2 O loss can potentially occur from this side-chain, as an alternative to loss from the C-terminal free acid of the dipeptide. Infrared action spectra of the product ions along with quantum-chemical calculations unambiguously show that dehydration consistently produces fragment ions containing an oxazoline moiety. This contrasts with the common oxazolone structure that would result from dehydration at the C-terminus analogous to the common b/y dissociation forming regular b 2 -type sequence ions. The oxazoline product structure suggests a reaction mechanism involving water loss from the Ser/Thr side-chain with concomitant nucleophilic attack of the amide carbonyl oxygen at its β-carbon, forming an oxazoline ring. However, an extensive quantum-chemical investigation comparing the potential energy surfaces for three entirely different dehydration reaction pathways indicates that it is actually the backbone amide oxygen atom that leaves as the water molecule.

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Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Water Loss from Protonated XxxSer and XxxThr Dipeptides Gives Oxazoline—Not Oxazolone—Product Ions

Kempkes

Geurts

Dijk

et al. 2020

J. Am. Soc. Mass Spectrom.

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“…23,24 The main advantages of IRMPD spectroscopy over methods based on PID in other spectral regions [25][26][27][28][29][30][31] is that the IR spectral signatures allow the discrimination of functional groups, the analysis of conformational isomers and the identification of protonation/ coordination sites, especially when supported by theoretical calculations. 32,33 Consequently, IRMPD experiments have been used in an extensive number of systems and analytical applications, [34][35][36][37][38][39] from biomolecules, 40-42 drugs [43][44][45] and metabolites [46][47][48][49] to the evaluation of catalysis and reaction mechanisms, 19,[50][51][52][53][54][55][56] nanocalorimetry determinations 57,58 and in studies evaluating the electrospray ionization process 59 and aerosol composition. 60 Optical parametric oscillators (OPOs) coupled to optical parametric amplifiers (OPAs) deliver infrared radiation in the 2000-4500 cm −1 frequency range, allowing the evaluation of higher frequency modes such as O-H and N-H stretches.…”

Section: Introductionmentioning

confidence: 99%

Development of a photoinduced fragmentation ion trap for infrared multiple photon dissociation spectroscopy

Penna

Cervi

Rodrigues‐Oliveira

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale Methods for isomer discrimination by mass spectroscopy are of increasing interest. Here we describe the development of a three‐dimensional ion trap for infrared multiple photon dissociation (IRMPD) spectroscopy that enables the acquisition of the infrared spectrum of selected ions in the gas phase. This system is suitable for the study of a myriad of chemical systems, including isomer mixtures. Methods A modified three‐dimensional ion trap was coupled to a CO2 laser and an optical parametric oscillator/optical parametric amplifier (OPO/OPA) system operating in the range 2300 to 4000 cm−1. Density functional theory vibrational frequency calculations were carried out to support spectral assignments. Results Detailed descriptions of the interface between the laser and the mass spectrometer, the hardware to control the laser systems, the automated system for IRMPD spectrum acquisition and data management are presented. The optimization of the crystal position of the OPO/OPA system to maximize the spectroscopic response under low‐power laser radiation is also discussed. Conclusions OPO/OPA and CO2 laser‐assisted dissociation of gas‐phase ions was successfully achieved. The system was validated by acquiring the IRMPD spectra of model species and comparing with literature data. Two isomeric alkaloids of high economic importance were characterized to demonstrate the potential of this technique, which is now available as an open IRMPD spectroscopy facility in Brazil.

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Energetics and mechanisms for decomposition of cationized amino acids and peptides explored using guided ion beam tandem mass spectrometry

Armentrout

2021

Mass Spectrometry Reviews

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Fragmentation studies of cationized amino acids and small peptides as studied using guided ion beam tandem mass spectrometry (GIBMS) are reviewed. After a brief examination of the key attributes of the GIBMS approach, results for a variety of systems are examined, compared, and contrasted. Cationization of amino acids, diglycine, and triglycine with alkali cations generally leads to dissociations in which the intact biomolecule is lost. Exceptions include most lithiated species as well as a few examples for sodiated and one example for potassiated species. Like the lithiated species, cationization by protons leads to numerous dissociation channels. Results for protonated glycine, cysteine, asparagine, diglycine, and a series of tripeptides are reviewed, along with the thermodynamic consequences that can be gleaned. Finally, the important physiological process of the deamidation of asparagine (Asn) residues is explored by the comparison of five dipeptides in which the C‐terminal partner (AsnXxx) is altered. The GIBMS thermochemistry is shown to correlate well with kinetic results from solution phase studies.

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Ion spectroscopy and guided ion beam studies of protonated asparaginyl-threonine decomposition: Influence of a hydroxyl containing C-Terminal residue on deamidation processes

Cited by 7 publications

References 54 publications

Water Loss from Protonated XxxSer and XxxThr Dipeptides Gives Oxazoline—Not Oxazolone—Product Ions

Water Loss from Protonated XxxSer and XxxThr Dipeptides Gives Oxazoline—Not Oxazolone—Product Ions

Development of a photoinduced fragmentation ion trap for infrared multiple photon dissociation spectroscopy

Energetics and mechanisms for decomposition of cationized amino acids and peptides explored using guided ion beam tandem mass spectrometry

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