Spontaneous Isomerization of Peptide Cation Radicals Following Electron Transfer Dissociation Revealed by UV-Vis Photodissociation Action Spectroscopy

Overview

Journal J Am Soc Mass Spectrom

Specialty Chemistry

Date 2018 Jan 18

PMID 29340957

Citations 2

Authors

Naruaki Imaoka

Camille Houferak

Megan P Murphy

Huong T H Nguyen

Andy Dang

Frantisek Turecek

Affiliations

Soon will be listed here.

Abstract

Peptide cation radicals of the z-type were produced by electron transfer dissociation (ETD) of peptide dications and studied by UV-Vis photodissociation (UVPD) action spectroscopy. Cation radicals containing the Asp (D), Asn (N), Glu (E), and Gln (Q) residues were found to spontaneously isomerize by hydrogen atom migrations upon ETD. Canonical N-terminal [z + H] fragment ion-radicals of the R-CH-CONH- type, initially formed by N-C bond cleavage, were found to be minor components of the stable ion fraction. Vibronically broadened UV-Vis absorption spectra were calculated by time-dependent density functional theory for several [DAAR + H] isomers and used to assign structures to the action spectra. The potential energy surface of [DAAR + H] isomers was mapped by ab initio and density functional theory calculations that revealed multiple isomerization pathways by hydrogen atom migrations. The transition-state energies for the isomerizations were found to be lower than the dissociation thresholds, accounting for the isomerization in non-dissociating ions. The facile isomerization in [XAAR + H] ions (X = D, N, E, and Q) was attributed to low-energy intermediates having the radical defect in the side chain that can promote hydrogen migration along backbone C positions. A similar side-chain mediated mechanism is suggested for the facile intermolecular hydrogen migration between the c- and [z + H]-ETD fragments containing Asp, Asn, Glu, and Gln residues. Graphical Abstract ᅟ.

Citing Articles

Spectroscopic Characterization of an Extensive Set of c-Type Peptide Fragment Ions Formed by Electron Transfer Dissociation Suggests Exclusive Formation of Amide Isomers.

Kempkes L, Martens J, Berden G, Oomens J J Phys Chem Lett. 2018; 9(22):6404-6411.

PMID: 30343579 PMC: 6240889. DOI: 10.1021/acs.jpclett.8b02850.

w-Type ions formed by electron transfer dissociation of Cys-containing peptides investigated by infrared ion spectroscopy.

Kempkes L, Martens J, Berden G, Oomens J J Mass Spectrom. 2018; 53(12):1207-1213.

PMID: 30281881 PMC: 6283004. DOI: 10.1002/jms.4298.

References

Chung T, Hui R, Ledvina A, Coon J, Turecek F . Cascade dissociations of peptide cation-radicals. Part 1. Scope and effects of amino acid residues in penta-, nona-, and decapeptides. J Am Soc Mass Spectrom. 2012; 23(8):1336-50. PMC: 3619428. DOI: 10.1007/s13361-012-0408-9. View

Turecek F . N[bond]C(alpha) bond dissociation energies and kinetics in amide and peptide radicals. Is the dissociation a non-ergodic process?. J Am Chem Soc. 2003; 125(19):5954-63. DOI: 10.1021/ja021323t. View

Turecek F . Benchmarking Electronic Excitation Energies and Transitions in Peptide Radicals. J Phys Chem A. 2015; 119(39):10101-11. DOI: 10.1021/acs.jpca.5b06235. View

Nguyen H, Andrikopoulos P, Bim D, Rulisek L, Dang A, Turecek F . Radical Reactions Affecting Polar Groups in Threonine Peptide Ions. J Phys Chem B. 2017; 121(27):6557-6569. DOI: 10.1021/acs.jpcb.7b04661. View

Chung T, Turecek F . Backbone and side-chain specific dissociations of z ions from non-tryptic peptides. J Am Soc Mass Spectrom. 2010; 21(8):1279-95. DOI: 10.1016/j.jasms.2010.02.018. View

OConnor P, Lin C, Cournoyer J, Pittman J, Belyayev M, Budnik B . Long-lived electron capture dissociation product ions experience radical migration via hydrogen abstraction. J Am Soc Mass Spectrom. 2006; 17(4):576-585. DOI: 10.1016/j.jasms.2005.12.015. View

Savitski M, Kjeldsen F, Nielsen M, Zubarev R . Hydrogen rearrangement to and from radical z fragments in electron capture dissociation of peptides. J Am Soc Mass Spectrom. 2006; 18(1):113-20. DOI: 10.1016/j.jasms.2006.09.008. View

Pepin R, Turecek F . Kinetic ion thermometers for electron transfer dissociation. J Phys Chem B. 2015; 119(7):2818-26. DOI: 10.1021/jp510244d. View

Shaffer C, Martens J, Marek A, Oomens J, Turecek F . Photoleucine Survives Backbone Cleavage by Electron Transfer Dissociation. A Near-UV Photodissociation and Infrared Multiphoton Dissociation Action Spectroscopy Study. J Am Soc Mass Spectrom. 2016; 27(7):1176-85. DOI: 10.1007/s13361-016-1390-4. View

10.

Chen X, Turecek F . The arginine anomaly: arginine radicals are poor hydrogen atom donors in electron transfer induced dissociations. J Am Chem Soc. 2006; 128(38):12520-30. DOI: 10.1021/ja063676o. View

11.

Turecek F, Syrstad E, Seymour J, Chen X, Yao C . Peptide cation-radicals. A computational study of the competition between peptide N-Calpha bond cleavage and loss of the side chain in the [GlyPhe-NH2 + 2H]+. cation-radical. J Mass Spectrom. 2003; 38(10):1093-104. DOI: 10.1002/jms.527. View

12.

Pepin R, Laszlo K, Peng B, Marek A, Bush M, Turecek F . Comprehensive analysis of Gly-Leu-Gly-Gly-Lys peptide dication structures and cation-radical dissociations following electron transfer: from electron attachment to backbone cleavage, ion-molecule complexes, and fragment separation. J Phys Chem A. 2013; 118(1):308-24. DOI: 10.1021/jp411100c. View

13.

Syka J, Coon J, Schroeder M, Shabanowitz J, Hunt D . Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry. Proc Natl Acad Sci U S A. 2004; 101(26):9528-33. PMC: 470779. DOI: 10.1073/pnas.0402700101. View

14.

Turecek F, Julian R . Peptide radicals and cation radicals in the gas phase. Chem Rev. 2013; 113(8):6691-733. DOI: 10.1021/cr400043s. View

15.

Nguyen H, Turecek F . Near-UV Photodissociation of Tryptic Peptide Cation Radicals. Scope and Effects of Amino Acid Residues and Radical Sites. J Am Soc Mass Spectrom. 2017; 28(7):1333-1344. DOI: 10.1007/s13361-016-1586-7. View

16.

Sobczyk M, Anusiewicz I, Berdys-Kochanska J, Sawicka A, Skurski P, Simons J . Coulomb-assisted dissociative electron attachment: application to a model peptide. J Phys Chem A. 2006; 109(1):250-8. DOI: 10.1021/jp0463114. View

17.

Ledvina A, Chung T, Hui R, Coon J, Turecek F . Cascade dissociations of peptide cation-radicals. Part 2. Infrared multiphoton dissociation and mechanistic studies of z-ions from pentapeptides. J Am Soc Mass Spectrom. 2012; 23(8):1351-63. PMC: 3619414. DOI: 10.1007/s13361-012-0409-8. View

18.

Barbatti M, Aquino A, Lischka H . The UV absorption of nucleobases: semi-classical ab initio spectra simulations. Phys Chem Chem Phys. 2010; 12(19):4959-67. DOI: 10.1039/b924956g. View

19.

Ledvina A, Coon J, Turecek F . Competitive Hydrogen Atom Migrations Accompanying Cascade Dissociations of Peptide Cation-Radicals of the Type. Int J Mass Spectrom. 2015; 377:44-53. PMC: 4380023. DOI: 10.1016/j.ijms.2014.02.015. View

20.

Stewart J . Optimization of parameters for semiempirical methods V: modification of NDDO approximations and application to 70 elements. J Mol Model. 2007; 13(12):1173-213. PMC: 2039871. DOI: 10.1007/s00894-007-0233-4. View