title: Peptide dimethylation: fragmentation control via distancing the dimethylamino group.
abstract: Direct reductive methylation of peptides is a common method for quantitative proteomics. It is an active derivatization technique; with participation of the dimethylamino group, the derivatized peptides preferentially release intense a1 ions. The advantageous generation of a1 ions for quantitative proteomic profiling, however, is not desirable for targeted proteomic quantitation using multiple reaction monitoring mass spectrometry; this mass spectrometric method prefers the derivatizing group to stay with the intact peptide ions and multiple fragments as passive mass tags. This work investigated collisional fragmentation of peptides whose amine groups were derivatized with five linear ω-dimethylamino acids, from 2-(dimethylamino)-acetic acid to 6-(dimethylamino)-hexanoic acid. Tandem mass spectra of the derivatized tryptic peptides revealed different preferential breakdown pathways. Together with energy resolved mass spectrometry, it was found that shutting down the active participation of the terminal dimethylamino group in fragmentation of derivatized peptides is possible. However, it took a separation of five methylene groups between the terminal dimethylamino group and the amide formed upon peptide derivatization. For the first time, the gas-phase fragmentation of peptides derivatized with linear ω-dimethylamino acids of systematically increasing alkyl chain lengths is reported.
authors.affiliation: Department of Chemistry, University of Connecticut, Storrs, CT, 06269, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: McShane
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shen
authors.forename: Mary Joan
authors.initials: MJ
authors.lastname: Castillo
authors.forename: Xudong
authors.initials: X
authors.lastname: Yao
mesh_terms: D004123:Dimethylamines / Q000737:chemistry*; D007477:Ions / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods*; D008745:Methylation; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D040901:Proteomics / Q000379:methods*
chemical_list: D004123:Dimethylamines; D007477:Ions; D010446:Peptide Fragments; D010455:Peptides
references.citation: Anal Chem. 2012 Aug 21;84(16):7188-94
references.pmid: 22881393
references.citation: Nat Protoc. 2009;4(4):484-94
references.pmid: 19300442
references.citation: Anal Chem. 2004 Apr 1;76(7):2083-94
references.pmid: 15053674
references.citation: Mass Spectrom Rev. 2009 Jul-Aug;28(4):640-54
references.pmid: 19338048
references.citation: J Mass Spectrom. 2009 May;44(5):821-31
references.pmid: 19301359
references.citation: J Am Soc Mass Spectrom. 2007 Aug;18(8):1414-22
references.pmid: 17543534
references.citation: J Mass Spectrom. 2008 Oct;43(10):1301-19
references.pmid: 18819114
references.citation: Proteomics. 2010 Sep;10(17):3108-16
references.pmid: 20661955
references.citation: Mol Cell Proteomics. 2010 Sep;9(9):1885-97
references.pmid: 20382981
references.citation: Anal Chem. 2005 Dec 1;77(23):7783-95
references.pmid: 16316189
references.citation: J Am Chem Soc. 2010 Nov 17;132(45):16006-16
references.pmid: 20977217
references.citation: Anal Chem. 2013 Feb 19;85(4):2478-85
references.pmid: 23316706
references.citation: Anal Bioanal Chem. 2012 Sep;404(4):991-1009
references.pmid: 22644145
references.citation: Anal Chem. 2010 Dec 15;82(24):10116-24
references.pmid: 21090646
references.citation: Anal Chem. 2011 Jun 15;83(12):4427-39
references.pmid: 21495688
references.citation: J Am Soc Mass Spectrom. 2001 Mar;12(3):288-95
references.pmid: 11281604
references.citation: Angew Chem Int Ed Engl. 2008;47(13):2463-5
references.pmid: 18300222
references.citation: J Proteome Res. 2013 Sep 6;12(9):4089-100
references.pmid: 23898821
references.citation: Mol Cell Proteomics. 2013 Sep;12(9):2623-39
references.pmid: 23689285
references.citation: Anal Chem. 2012 Sep 4;84(17):7469-78
references.pmid: 22880955
references.citation: Rapid Commun Mass Spectrom. 2001;15(16):1457-72
references.pmid: 11507760
references.citation: J Mass Spectrom. 1996 Nov;31(11):1237-43
references.pmid: 8946732
references.citation: Anal Chem. 2013 Nov 19;85(22):10658-63
references.pmid: 24180428
references.citation: J Mass Spectrom. 2000 Jun;35(6):683-8
references.pmid: 10862119
references.citation: Chem Commun (Camb). 2014 Feb 18;50(14):1708-10
references.pmid: 24394284
references.citation: J Proteome Res. 2005 Jan-Feb;4(1):101-8
references.pmid: 15707364
references.citation: Anal Chem. 2010 Jan 1;82(1):23-7
references.pmid: 19904916
references.citation: Mol Cell Proteomics. 2004 Dec;3(12):1154-69
references.pmid: 15385600
references.citation: Mol Cell Proteomics. 2013 Nov;12(11):3360-9
references.pmid: 23882030
references.citation: Anal Chem. 2003 Dec 15;75(24):6843-52
references.pmid: 14670044
references.citation: Anal Chem. 2009 Aug 1;81(15):6438-48
references.pmid: 19572545
references.citation: Rapid Commun Mass Spectrom. 2006;20(10):1525-30
references.pmid: 16642461
references.citation: J Proteome Res. 2009 Nov;8(11):5347-55
references.pmid: 19754192
references.citation: J Proteome Res. 2014 Mar 7;13(3):1494-501
references.pmid: 24417624
references.citation: J Proteome Res. 2008 Aug;7(8):3525-34
references.pmid: 18630974
references.citation: Anal Chem. 2013 May 21;85(10):5129-37
references.pmid: 23638792