Development of a screening technique for noncovalent complex formation between guanidinium- and phosphonate-functionalized amino acids by electrospray ionization ion trap mass spectrometry: assessing ionization and functional group interaction

Schug, Kevin A.; Lindner, Wolfgang

doi:10.1016/j.ijms.2004.04.012

Cited by 15 publications

(11 citation statements)

References 57 publications

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“…Such interactions have been considered to explain the stability of arginine-phosphopeptide ion clusters [46][47][48] but do not seem to play a role in isolated peptide ions in which the phosphate group is neutral. This is presumably due to the donor-acceptor nature of the neutral phosphate group, where the P = O oxygen atom serves as a p-electron donor in solvating acidic protons of the peptide groups, and the acidic P-OH protons are internally solvated by suitable electron donors from the peptide amide or carboxyl groups.…”

Section: Precursor Ion Structuresmentioning

confidence: 99%

Dipole-Guided Electron Capture Causes Abnormal Dissociations of Phosphorylated Pentapeptides

Moss

Chung

Wyer

et al. 2011

J. Am. Soc. Mass Spectrom.

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Electron transfer and capture mass spectra of a series of doubly charged ions that were phosphorylated pentapeptides of a tryptic type (pS,A,A,A,R) showed conspicuous differences in dissociations of charge-reduced ions. Electron transfer from both gaseous cesium atoms at 100 keV kinetic energies and fluoranthene anion radicals in an ion trap resulted in the loss of a hydrogen atom, ammonia, and backbone cleavages forming complete series of sequence z ions. Elimination of phosphoric acid was negligible. In contrast, capture of lowenergy electrons by doubly charged ions in a Penning ion trap induced loss of a hydrogen atom followed by elimination of phosphoric acid as the dominant dissociation channel. Backbone dissociations of charge-reduced ions also occurred but were accompanied by extensive fragmentation of the primary products. z-Ions that were terminated with a deaminated phosphoserine radical competitively eliminated phosphoric acid and H 2 PO 4 radicals. A mechanism is proposed for this novel dissociation on the basis of a computational analysis of reaction pathways and transition states. Electronic structure theory calculations in combination with extensive molecular dynamics mapping of the potential energy surface provided structures for the precursor phosphopeptide dications. Electron attachment produces a multitude of low lying electronic states in charge-reduced ions that determine their reactivity in backbone dissociations and H-atom loss. The predominant loss of H atoms in ECD is explained by a distortion of the Rydberg orbital space by the strong dipolar field of the peptide dication framework. The dipolar field steers the incoming electron to preferentially attach to the positively charged arginine side chain to form guanidinium radicals and trigger their dissociations.

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Section: Precursor Ion Structuresmentioning

confidence: 99%

Dipole-Guided Electron Capture Causes Abnormal Dissociations of Phosphorylated Pentapeptides

Moss

Chung

Wyer

et al. 2011

J. Am. Soc. Mass Spectrom.

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“…The ability of ESI-MS to detect a specific noncovalent complex depends on factors related to both its solution-phase and gas-phase properties. Schug and Linder define a relationship, termed relative transmission factor, as "the relationship between measured ion intensities and the initial concentration of each component" [54,55]. The relative transmission factor will depend on the binding affinities the molecular partners have for each other in solution, and this in turn is influenced by the structures of the components and the types and strengths of the forces holding them together in solution.…”

Section: Unusual Stability Of Gas Phase Charge-charge Interactionsmentioning

confidence: 99%

Mass spectrometry of protein-ligand complexes: Enhanced gas-phase stability of ribonuclease-nucleotide complexes

Yin

Xie

Loo

2008

J. Am. Soc. Mass Spectrom.

118

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Noncovalent protein-ligand complexes are readily detected by electrospray ionization mass spectrometry (ESI-MS). Ligand binding stoichiometry can be determined easily by the ESI-MS method. The ability to detect noncovalent protein-ligand complexes depends, however, on the stability of the complexes in the gas-phase environment. Solution binding affinities may or may not be accurate predictors of their stability in vacuo. Complexes composed of cytidine nucleotides bound to ribonuclease A (RNase A) and ribonuclease S (RNase S) were detected by ESI-MS and were further analyzed by MS/MS. RNase A and RNase S share similar structures and biological activity. Subtilisin-cleavage of RNase A yields an S-peptide and an S-protein; the S-peptide and S-protein interact through hydrophobic interactions with a solution binding constant in the nanomolar range to generate an active RNase S. Cytidine nucleotides bind to the ribonucleases through electrostatic interactions with a solution binding constant in the micromolar range. Collisionally activated dissociation (CAD) of the 1:1 RNase A-CDP and CTP complexes yields cleavage of the covalent phosphate bonds of the nucleotide ligands, releasing CMP from the complex. CAD of the RNase S-CDP and CTP complexes dissociates the S-peptide from the remaining S-protein/nucleotide complex; further dissociation of the S-protein/nucleotide complex fragments a covalent phosphate bond of the nucleotide with subsequent release of CMP. Despite a solution binding constant favoring the S-protein/S-peptide complex, CDP/CTP remains electrostatically bound to the S-protein in the gas-phase dissociation experiment. This study highlights the intrinsic stability of electrostatic interactions in the gas phase and the significant differences in solution and gas-phase stabilities of noncovalent complexes that can result.

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“…Another feature of this study is intended to complement a previous investigation on the reaction of a modified arginine with some dicarbonyls 27. Furthermore, the proton‐loving guanidino group is present in a vast number of naturally occurring and synthetic interaction systems that are biologically and pharmacologically relevant 28, 29. This unit function, composed of a Y‐shaped fork with planar geometry, is known to be capable of both directed hydrogen bonding, and nondirected Coulombic interactions with complementary groups 28, 29.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the proton‐loving guanidino group is present in a vast number of naturally occurring and synthetic interaction systems that are biologically and pharmacologically relevant 28, 29. This unit function, composed of a Y‐shaped fork with planar geometry, is known to be capable of both directed hydrogen bonding, and nondirected Coulombic interactions with complementary groups 28, 29. All these factors increased our motivation to study the reactivity of the guanidino group under the reaction conditions that may elucidate the behavior of its reaction center in vitro and in vivo .…”

Section: Introductionmentioning

confidence: 99%

Towards the control and inhibition of glycation—the role of the guanidine reaction center with aldehydic and diketonic dicarbonyls. A mass spectrometry study

2006

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Glycation of proteins by glucose and formation of end-stage adducts (AGEs, advanced glycation end products) has been implicated in pathological mechanisms associated with diabetic complications, macrovascular disease, chronic and renal insufficiency, Alzheimer's disease, and aging. Of the carbonyl containing compounds involved in this process, alpha-dicarbonyls have particular importance, being established as direct intermediates in the formation of well-known AGEs. The guanidino group, present in arginine residues, suffers direct modifications by sugars and its derivatives, and is considered to be an important chemical basis, targeting the control and inhibition of glycation. Seven dicarbonyl compounds, aldehydic and diketonic, were reacted with guanidine, in an attempt to establish structure/activity relationships. Electrospray mass spectrometry, together with tandem mass spectrometry, was used to identify and characterize the reaction products. The reactivity of guanidine was found to vary with the dicarbonyls used. For glyoxal, a high amount of dihydroxyimidazolidine was formed, whereas for methylglyoxal, dihydroxyimidazolidine was slowly converted into hydroimidazolone. Interestingly, aqueous guanidine was found to prevent argpyrimidine formation. The formation of several amine-dicarbonyl moieties was observed for the larger alkyl-diketonic dicarbonyls reaction systems, in particular. Molecular structures, bearing a polar chain, of an imidazole ring, and a nonpolar one, of alkyl groups, located at both sides of the imidazole rings, were attributed to these moieties. Gas-phase experiments suggested that the larger alkyl groups have a preference for being located at one of the sides of the imidazole rings. Moreover, the referred amine-dicarbonyl moieties are formed via (dihydroxyimidazolidine - 2H2O) moieties. The latter (dihydroxyimidazolidine - 2H2O) moieties are formed in high amounts in the larger alkyl-diketonic dicarbonyl reactions. Since these moieties react with dicarbonyl molecules, and react even faster with already modified amine functions, we can foresee that these species may be useful for controlling and inhibiting glycation of larger biomolecules, such as proteins.

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Development of a screening technique for noncovalent complex formation between guanidinium- and phosphonate-functionalized amino acids by electrospray ionization ion trap mass spectrometry: assessing ionization and functional group interaction

Cited by 15 publications

References 57 publications

Dipole-Guided Electron Capture Causes Abnormal Dissociations of Phosphorylated Pentapeptides

Dipole-Guided Electron Capture Causes Abnormal Dissociations of Phosphorylated Pentapeptides

Mass spectrometry of protein-ligand complexes: Enhanced gas-phase stability of ribonuclease-nucleotide complexes

Towards the control and inhibition of glycation—the role of the guanidine reaction center with aldehydic and diketonic dicarbonyls. A mass spectrometry study

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