The importance of charge-separation reactions in tandem mass spectrometry of doubly protonated angiotensin II formed by electrospray ionization: Experimental considerations and structural implications

Adams, Jeanette; Strobel, Fred; Reiter, Alex; Sullards, M. Cameron

doi:10.1016/1044-0305(95)00604-4

Cited by 34 publications

(41 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results showed little variation with collision energy at the lower collision energies which were used to derive the data of ties. In agreement with the analysis of Zubarev and coworkers [11] symmetric cleavage of the second amide bond dominates for smaller peptides but decreases substantially in importance as the peptide size increases and is not the dominant cleavage mode for doublyprotonated (Ala) 10 His. Paizs and coworkers [13] also observed that symmetric cleavage of the second amide bond was the dominant fragmentation mode for doublyprotonated (Gly) 5 Arg.…”

Section: Resultssupporting

confidence: 88%

“…In all cases these asymmetric amide bond cleavages occur near the N-terminus of the peptide. Thus, (Ala) 5 His shows a weak signal for y 5 ϩ2 , (Ala) 6 His shows weak signals for y 5 ϩ2 and y 6 ϩ2 , (Ala) 7 His shows weak signals for y 6 ϩ2 and y 7 ϩ2 , (Ala) 8 His shows weak signals for y 7 ϩ2 and y 8 ϩ2 while (Ala) 10 His shows a signal for y 9 ϩ2 and a very weak signal at m/z 398 corresponding to y 10 ϩ2 . The primary b and y ions undergo further fragmentation, particularly at higher collision energies.…”

Section: Resultsmentioning

confidence: 98%

“…

…”

mentioning

confidence: 99%

“…On the other hand, despite the importance of the fragmentation chemistry of doubly-protonated tryptic peptides in proteomics, much less is known in detail concerning the fragmentation reactions of such species. A common fragmentation reaction of doublyprotonated peptides is charge separation in which amide bond cleavage leads to complementary singlycharged b and y ions [7][8][9][10]. Recently, Zubarev and coworkers [11] have carried out a statistical analysis of a large database of CID spectra of doubly-protonated tryptic peptides.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Charge-separation reactions of doubly-protonated peptides: Effect of peptide chain length

Harrison

2009

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

The collision induced dissociation of doubly-protonated (Ala) x His (x ϭ 5, 6,7,8,10) peptides have been studied. The major fragmentation reactions observed are symmetrical amide bond cleavages to give the complementary b m and y N-m ions, where N is the total number of residues in the peptide. Minor asymmetric cleavage to give doubly-protonated y ions also is observed, involving cleavage near the N-terminus. The shorter peptides (x ϭ 5, 6, 7) show major cleavage of the second amide bond to yield b 2 and y N-2 ions, while (Ala) 10 His shows major symmetrical cleavage at the fourth and fifth amide bonds. T andem mass spectrometry has become a widely used method for deriving sequence information for peptides and proteins [1][2][3]. Protein identification in the field of proteomics most often involves protein digestion by trypsin, with identification and sequencing of the peptides produced by collision-induced dissociation of the singly-or multiply-protonated peptides resulting from soft ionization methods such as electrospray ionization [4]. Trypsin usually cleaves proteins C-terminal to arginine or lysine with the result that the peptides produced have a highly basic residue at the C-terminus. Such basic residues will localize a proton on the basic side chain [5], which often leads to fragmentation associated with the basic site rather than cleavage along the peptide backbone that is necessary for peptide sequencing. As a consequence fragmentation of doubly-or multiply-charged peptides in which there is a mobile proton [5] has been found to provide more complete sequence information.There have been many detailed studies of the dissociation chemistry of singly-protonated nontryptic peptides; these studies have been summarized in a recent review [6]. On the other hand, despite the importance of the fragmentation chemistry of doubly-protonated tryptic peptides in proteomics, much less is known in detail concerning the fragmentation reactions of such species. A common fragmentation reaction of doublyprotonated peptides is charge separation in which amide bond cleavage leads to complementary singlycharged b and y ions [7][8][9][10]. Recently, Zubarev and coworkers [11] have carried out a statistical analysis of a large database of CID spectra of doubly-protonated tryptic peptides. They found that the charge separation spectra fell into two well separated statistical classes. Class I CID spectra were dominated by the y N-2 ion signal (and, presumably, the corresponding b 2 ion) where N is the number of amino acid residues in the peptide. By contrast, Class II CID spectra showed other y ions as the most abundant charge-separation products. There is some evidence from their analysis that cleavage of the second amide bond to form y N-2 is particularly important for smaller peptides and decreases in relative importance with increasing size of the peptide. It appeared of interest to study a series of peptides where the only variable is the number of residues in the peptide so that the effect of chain length can be separated...

show abstract

Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 98%

“…

…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Charge-separation reactions of doubly-protonated peptides: Effect of peptide chain length

Harrison

2009

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

show abstract

“…10. This indicates that the y 2 /b 5 ion pair is complementary, consistent with conclusions for the y 2 /b 5 ions of doubly-protonated angiotensin II (DRVYIHPF) using kinetic energy release distributions (KERDs) [45]. While scrambling of the deuterium atoms before or during the fragmentation event cannot be ruled-out, the partitioning of the deuterium atoms demonstrates that both fragment ions are being formed by the same mechanism.…”

Section: Fragmentation Of [Rvyifpf + 2h] 2+ Ion Populations Labeled Bsupporting

confidence: 75%

Fragmentation of doubly-protonated peptide ion populations labeled by H/D exchange with CD3OD

Herrmann

Kuppannan

Wysocki

2006

International Journal of Mass Spectrometry

View full text Add to dashboard Cite

Doubly-protonated bradykinin (RPPGFSPFR) and an angiotensin III analogue (RVYIFPF) were subjected to hydrogen/deuterium (H/D) exchange with CD 3 OD in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. A bimodal distribution of deuterium incorporation was present for bradykinin after H/D exchange for 90 s at a CD 3 OD pressure of 4 × 10 −7 Torr, indicating the existence of at least two distinct populations. Bradykinin ion populations corresponding to 0-2 and 5-11 deuteriums (i.e., D 0 , D 1 , D 2 , D 5 , D 6 , D 7 , D 8 , D 9 , D 10 , and D 11 ) were each monoisotopically selected and fragmented via sustained off-resonance irradiation (SORI) collision-induced dissociation (CID). The D 0 -D 2 ion populations, which correspond to the slower exchanging population, consistently require lower SORI amplitude to achieve a similar precursor ion survival yield as the faster-reacting (D 5 -D 11 ) populations. These results demonstrate that conformation/ protonation motif has an effect on fragmentation efficiency for bradykinin. Also, the partitioning of the deuterium atoms into fragment ions suggests that the C-terminal arginine residue exchanges more rapidly than the N-terminal arginine. Total deuterium incorporation in the b 1 /y 8 and b 2 /y 7 ion pairs matches very closely the theoretical values for all ion populations studied, indicating that the ions of a complementary pair are likely formed during the same fragmentation event, or that no scrambling occurs upon SORI. Deuterium incorporation into the y 1 /a 8 pseudo-ion pair does not closely match the expected theoretical values. The other peptide, doubly-protonated RVYIFPF, has a trimodal distribution of deuterium incorporation upon H/D exchange with CD 3 OD at a pressure of 1 × 10 −7 Torr for 600 s, indicating at least three distinct ion populations. After 90 s of H/D exchange where at least two distinct populations are detected, the D 0 -D 7 ion populations were monoisotopically selected and fragmented via SORI-CID over a range of SORI amplitudes. The precursor ion survival yield as a function of SORI amplitude falls into two distinct behaviors corresponding to slower-and faster-reacting ion populations. The slower-reacting population requires larger SORI amplitudes to achieve the same precursor ion survival yield as the faster exchanging population. Total deuterium incorporation into the y 2 /b 5 ion pairs matches closely the theoretical values over all ion populations and SORI amplitudes studied. This result indicates the y 2 and b 5 ions are likely formed by the same mechanism over the SORI amplitudes studied.

show abstract

Proton Transfer Reactivity of Large Multiply Charged Ions

Williams

1996

J. Mass Spectrom.

186

View full text Add to dashboard Cite

Charge-charge interactions dramatically influence the dissociation and proton transfer reactivity of large multiply protonated ions. In combination with tandem mass spectrometry, proton transfer reactions have been used to determine the charge state of an ion and to increase the effective mass resolution of electrospray ionization mass spectra. A model for the proton transfer reactivity of multiply protonated ions, in which protons are assigned to specific sites in an ion based on the intrinsic reactivity of the site and the sum of point-charge Coulomb interactions between charges, is discussed. In combination with experimentally measured rates of proton transfer to bases of known gas-phase basicity, information about the intramolecular electrostatic interactions, gas-phase ion conformation and maximum charge state of an ion produced by electrospray ionization can be obtained.

show abstract

The importance of charge-separation reactions in tandem mass spectrometry of doubly protonated angiotensin II formed by electrospray ionization: Experimental considerations and structural implications

Cited by 34 publications

References 83 publications

Charge-separation reactions of doubly-protonated peptides: Effect of peptide chain length

Charge-separation reactions of doubly-protonated peptides: Effect of peptide chain length

Fragmentation of doubly-protonated peptide ion populations labeled by H/D exchange with CD3OD

Proton Transfer Reactivity of Large Multiply Charged Ions

Contact Info

Product

Resources

About