This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The primary N-C? bond cleavage by electron capture dissociation (ECD) or electron transfer dissociation (ETD) of a multiply charged peptide ion produces an even electron c ion and an odd electron z+ ion, the latter of which contains a radical which may initiate secondary fragmentations. These secondary fragmentations are all charge remote fragmentations (CRFs), because they do not involve the direct participation of a charged site. Secondary fragment ions generated by CRFs can be very useful for peptide structural analysis, as demonstrated by the utility of w-ions in isomer differentiation, but their presence may also complicate the spectral interpretation. In this study, secondary fragmentation of several synthetic peptides was studied by both ECD and ETD. In ECD, in addition to c and z+ ion formations, charge remote fragmentations (CRF) of z+ ions were abundant, resulting in internal fragment formation or partial/entire side chain losses from amino acids, sometimes several residues away from the backbone cleavage site, and to some extent multiple side chain losses. These secondary cleavages were postulated to be initiated by hydrogen abstraction at the ?-, ?-, or ?-position of the amino acid side chain, after the initial backbone cleavage in ECD. In comparison, ETD generates fewer CRF fragments than ECD, possibly due to small energy deposition and stabilization of radicals in z+ ions by collisional cooling in ETD. This secondary cleavage study will facilitate ECD/ETD spectra interpretation, and help de novo sequencing and database searching. These results were published in a recent J. Am. Soc. Mass Spectrom. article.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR010888-15
Application #
8365565
Study Section
Special Emphasis Panel (ZRG1-BCMB-H (40))
Project Start
2011-06-01
Project End
2012-08-09
Budget Start
2011-06-01
Budget End
2012-08-31
Support Year
15
Fiscal Year
2011
Total Cost
$16,920
Indirect Cost
Name
Boston University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
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Hu, Han; Khatri, Kshitij; Klein, Joshua et al. (2016) A review of methods for interpretation of glycopeptide tandem mass spectral data. Glycoconj J 33:285-96
Ji, Yuhuan; Bachschmid, Markus M; Costello, Catherine E et al. (2016) S- to N-Palmitoyl Transfer During Proteomic Sample Preparation. J Am Soc Mass Spectrom 27:677-85
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Yu, Xiang; Sargaeva, Nadezda P; Thompson, Christopher J et al. (2015) In-Source Decay Characterization of Isoaspartate and ?-Peptides. Int J Mass Spectrom 390:101-109
Steinhorn, Benjamin S; Loscalzo, Joseph; Michel, Thomas (2015) Nitroglycerin and Nitric Oxide--A Rondo of Themes in Cardiovascular Therapeutics. N Engl J Med 373:277-80
Walsh, Erica M; Niu, MengMeng; Bergholz, Johann et al. (2015) Nutlin-3 down-regulates retinoblastoma protein expression and inhibits muscle cell differentiation. Biochem Biophys Res Commun 461:293-9

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