Hydrogen-deuterium exchange of α-carbon protons and fragmentation pathways in N-methylated glycine and alanine-containing peptides derivatized by quaternary ammonium salts

Bąchor, Remigiusz; Kluczyk, Alicja; Stefanowicz, Piotr; Szewczuk, Zbigniew

doi:10.1002/jms.3371

Cited by 12 publications

(17 citation statements)

References 19 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, we observed that in the case of the α ‐C hydrogens of the N,N,N ‐trialkylglycine (betaine) residue in peptides, described by us previously , the H/D exchange occurs within 1 min, which suggests the effect of the quaternary ammonium group on the acidity of the α ‐C hydrogens . We have also found the possibility of such HDX at the α ‐C of the N ‐methyl alanine residue in peptides derivatized by a quaternary ammonium group .…”

Section: Introductionsupporting

confidence: 71%

See 1 more Smart Citation

Convenient preparation of deuterium‐labeled analogs of peptides containing N‐substituted glycines for a stable isotope dilution LC‐MS quantitative analysis

Bąchor

Dębowski

Łęgowska

et al. 2015

Journal of Peptide Science

Self Cite

View full text Add to dashboard Cite

N-substituted glycines constitute mimics of natural amino acids that are of great interest in the peptide-based drug development. Peptoids-oligo(N-substituted glycines) have been recently demonstrated to be highly active peptidomimetics in biological systems, resistant to proteolytic degradation. We developed a method of the deuterium labeling of peptidomimetics containing N-substituted glycine residues via H/D exchange of their α-carbon hydrogen atoms. The labeling was shown to be easy, inexpensive, and without the use of derivatization reagents or the need for a further purification. The deuterons introduced at the α-carbon atoms do not undergo a back exchange under acidic conditions during liquid chromatography mass spectrometry (LC-MS) analysis. The LC-MS analysis of a mixture of isotopologues revealed a co-elution of deuterated and nondeuterated forms of the peptidomimetics, which may be useful in the quantitative isotope dilution analysis of peptoids and other derivatives of N-substituted glycines.

show abstract

Section: Introductionsupporting

confidence: 71%

“…Such a procedure allowed one to observe the presence of deuterons introduced at the α ‐C. Based on our previous research , the α ‐C deuterons of N ‐methyl glycine and N ‐methyl alanine residues do not undergo the back exchange at acidic conditions.…”

Section: Resultsmentioning

confidence: 99%

Convenient preparation of deuterium‐labeled analogs of peptides containing N‐substituted glycines for a stable isotope dilution LC‐MS quantitative analysis

Bąchor

Dębowski

Łęgowska

et al. 2015

Journal of Peptide Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…Such results may suggest the different fragmentation mechanism during ESI‐MS/MS analysis of QCP conjugates. The fragmentation pathways observed for QCP may include the tertiary amine elimination according to the Hofmann elimination . This observation opens the possibility of application of the ions corresponding to the protonated cryptand amine as a reporter group during the tandem mass spectrometry analysis, especially multiple reaction monitoring.…”

Section: Resultsmentioning

confidence: 93%

Synthesis and mass spectrometry analysis of quaternary cryptando-peptidic conjugates

et al. 2015

Self Cite

View full text Add to dashboard Cite

The bicyclic amines in the form of cryptands, the crown ether analogs, were used in the synthesis of cryptando-peptidic conjugates with simultaneous formation of quaternary ammonium nitrogen moiety. A series of model cryptando-peptidic conjugates at the peptide N-terminus was efficiently prepared by the standard Fmoc solid phase synthesis. Tandem mass spectrometric analysis of the obtained conjugates has shown the specific fragmentation pattern during MS/MS experiment. The obtained cryptandic quaternary ammonium group undergoes the Hofmann elimination during collision-induced dissociation fragmentation followed by the ethoxyl group elimination. The presented quaternization of cryptands by iodoacetylated peptides is relatively easy and compatible with standard solid-phase peptide synthesis. Additionally, the applicability of such peptide derivatives and their isotopologues selectively deuterated at the α-carbon in the quantitative LC-MS analysis was analyzed.

show abstract

“…This resulted in a neutral ketene structure at the Nfragment and a y-type ion at the C-fragment. Their studies on deuterated QA-tagged oligosarcosine further showed that formation of y-ions involved the migration of a proton from the α-C-H bond of sarcosine residue [56]. For peptoids, the oxazolone B-ion is a quaternary ammonium cation.…”

Section: Fragmentation Mechanism: Y-ion Formationmentioning

confidence: 99%

“…This study suggested that the presence of the acidic N-H a bond was crucial for the formation of peptide-y-ions. Recently, Szewczuk and coworkers carried out a series of studies on the fragmentation pathways in N-substituted oligopeptides, including oligoproline and oligosarcosine, with a quaternary ammonium (QA) group tagged at the N-terminus [56,57]. These peptides did not contain backbone N-H groups.…”

Section: Fragmentation Mechanism: Y-ion Formationmentioning

confidence: 99%

Fragmentation Patterns and Mechanisms of Singly and Doubly Protonated Peptoids Studied by Collision Induced Dissociation

Ren¹,

Tian²,

Hossain³

et al. 2016

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

Abstract. Peptoids are peptide-mimicking oligomers consisting of N-alkylated glycine units. The fragmentation patterns for six singly and doubly protonated model peptoids were studied via collision-induced dissociation tandem mass spectrometry. The experiments were carried out on a triple quadrupole mass spectrometer with an electrospray ionization source. Both singly and doubly protonated peptoids were found to fragment mainly at the backbone amide bonds to produce peptoid B-type N-terminal fragment ions and Y-type C-terminal fragment ions. However, the relative abundances of B-versus Y-ions were significantly different. The singly protonated peptoids fragmented by producing highly abundant Y-ions and lesser abundant Bions. The Y-ion formation mechanism was studied through calculating the energetics of truncated peptoid fragment ions using density functional theory and by controlled experiments. The results indicated that Y-ions were likely formed by transferring a proton from the C-H bond of the N-terminal fragments to the secondary amine of the C-terminal fragments. This proton transfer is energetically favored, and is in accord with the observation of abundant Y-ions. The calculations also indicated that doubly protonated peptoids would fragment at an amide bond close to the N-terminus to yield a high abundance of low-mass B-ions and high-mass Y-ions. The results of this study provide further understanding of the mechanisms of peptoid fragmentation and, therefore, are a valuable guide for de novo sequencing of peptoid libraries synthesized via combinatorial chemistry.

show abstract

Hydrogen-deuterium exchange of α-carbon protons and fragmentation pathways in N-methylated glycine and alanine-containing peptides derivatized by quaternary ammonium salts

Cited by 12 publications

References 19 publications

Convenient preparation of deuterium‐labeled analogs of peptides containing N‐substituted glycines for a stable isotope dilution LC‐MS quantitative analysis

Convenient preparation of deuterium‐labeled analogs of peptides containing N‐substituted glycines for a stable isotope dilution LC‐MS quantitative analysis

Synthesis and mass spectrometry analysis of quaternary cryptando-peptidic conjugates

Fragmentation Patterns and Mechanisms of Singly and Doubly Protonated Peptoids Studied by Collision Induced Dissociation

Contact Info

Product

Resources

About