Selective cleavage upon ETD of peptides containing disulfide or nitrogen–nitrogen bonds

Bishop, Alex; Brodbelt, Jennifer S.

doi:10.1016/j.ijms.2014.07.024

Cited by 5 publications

(4 citation statements)

References 43 publications

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“…This pathway may contribute to the favored cleavage of disulfide bonds observed previously in ETD/ECD. 31 These reaction pathways may contribute to the products observed following supplemental activation of ETnoD products.…”

Section: Resultsmentioning

confidence: 99%

Leveraging Electron Transfer Dissociation for Site Selective Radical Generation: Applications for Peptide Epimer Analysis

Lyon

Beran

Julian

2017

J. Am. Soc. Mass Spectrom.

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Traditional electron-transfer dissociation (ETD) experiments operate through a complex combination of hydrogen abundant and hydrogen deficient fragmentation pathways, yielding c and z ions, side chains losses, and disulfide bond scission. Herein, a novel dissociation pathway is reported, yielding homolytic cleavage of carbon-iodine bonds via electronic excitation. This observation is very similar to photodissociation experiments where homolytic cleavage of carbon-iodine bonds has been utilized previously, but ETD-activation can be performed without addition of a laser to the mass spectrometer. Both loss of iodine and loss of hydrogen iodide are observed, with the abundance of the latter product being greatly enhanced for some peptides after additional collisional activation. These observations suggest a novel ETD fragmentation pathway involving temporary storage of the electron in a charge-reduced arginine side chain. Subsequent collisional activation of the peptide radical produced by loss of HI yields spectra dominated by radical-directed dissociation, which can be usefully employed for identification of peptide isomers, including epimers.

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Section: Resultsmentioning

confidence: 99%

Leveraging Electron Transfer Dissociation for Site Selective Radical Generation: Applications for Peptide Epimer Analysis

Lyon

Beran

Julian

2017

J. Am. Soc. Mass Spectrom.

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“…Both MALDI in-source decay − and electron transfer dissociation (ETD) − have been shown to yield fragment ions resulting from the cleavage of the disulfide bond. Hybrid ETD methods, including electron-transfer/CID and electron-transfer/higher energy collisional dissociation (EThcD), boost the generation of sequence-related fragment ions. , The capabilities of ultraviolet photodissociation (UVPD) for analysis of disulfide-bridged peptides have been explored. − 266 nm UVPD results in site-specific cleavage of disulfide bonds, offering higher confidence in peptide pairing and better characterization when combined with electron capture dissociation (ECD). , 193 nm UVPD has also achieved complete characterization of peptides containing complex disulfide bridges by integrating informative fragment ions resulting from cleavage of disulfide bridges with fragment ions retaining disulfide linkages . The ability of 193 nm UVPD to achieve high quality characterization without requiring MS 3 approaches represented a promising benchmark for analysis of disulfide- and diselenide-bridged peptides.…”

Section: Introductionmentioning

confidence: 99%

Integrated Top-Down and Bottom-Up Mass Spectrometry for Characterization of Diselenide Bridging Patterns of Synthetic Selenoproteins

et al. 2022

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With the rapid acceleration in the design and development of new biotherapeutics, ensuring consistent quality and understanding degradation pathways remain paramount, requiring an array of analytical methods including mass spectrometry. The incorporation of non-canonical amino acids, such as for synthetic selenoproteins, creates additional challenges. A comprehensive strategy to characterize selenoproteins should serve dual purposes of providing sequence confirmation and mapping of selenocysteine bridge locations and the identification of unanticipated side products. In the present study, a combined approach exploiting the benefits of both top-down and bottom-up mass spectrometry was developed. Both electron-transfer/higher-energy collision dissociation and 213 nm ultraviolet photodissociation were utilized to provide complementary information, allowing high quality characterization, localization of diselenide bridges for complex proteins, and the identification of previously unreported selenoprotein dimers.

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“…Depending upon the identity of the atom which has acquired such a positive region, the ensuing bonds are typically labeled as halogen [ 6 , 7 , 8 , 9 ], chalcogen [ 10 , 11 , 12 ], pnicogen [ 13 , 14 , 15 , 16 ], tetrel [ 17 , 18 , 19 , 20 ], triel [ 21 , 22 , 23 ], or aerogen bonds [ 24 , 25 , 26 , 27 ]. The underlying nature of these interactions have been the subject of considerable theoretical research, and have applications in fields such as crystal engineering [ 28 , 29 , 30 , 31 , 32 , 33 ], supramolecular chemistry [ 34 , 35 , 36 , 37 ], materials chemistry [ 38 , 39 ], and biochemistry [ 40 , 41 , 42 , 43 ]. A number of experimental works have generated an impressive database of crystalline structures which inspire detailed theoretical analyses.…”

Section: Introductionmentioning

confidence: 99%

Anion–Anion Interactions in Aerogen-Bonded Complexes. Influence of Solvent Environment

et al. 2021

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Ab initio calculations are applied to the question as to whether a AeX5− anion (Ae = Kr, Xe) can engage in a stable complex with another anion: F−, Cl−, or CN−. The latter approaches the central Ae atom from above the molecular plane, along its C5 axis. While the electrostatic repulsion between the two anions prevents their association in the gas phase, immersion of the system in a polar medium allows dimerization to proceed. The aerogen bond is a weak one, with binding energies less than 2 kcal/mol, even in highly polar aqueous solvent. The complexes are metastable in the less polar solvents THF and DMF, with dissociation opposed by a small energy barrier.

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Selective cleavage upon ETD of peptides containing disulfide or nitrogen–nitrogen bonds

Cited by 5 publications

References 43 publications

Leveraging Electron Transfer Dissociation for Site Selective Radical Generation: Applications for Peptide Epimer Analysis

Leveraging Electron Transfer Dissociation for Site Selective Radical Generation: Applications for Peptide Epimer Analysis

Integrated Top-Down and Bottom-Up Mass Spectrometry for Characterization of Diselenide Bridging Patterns of Synthetic Selenoproteins

Anion–Anion Interactions in Aerogen-Bonded Complexes. Influence of Solvent Environment

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