The gas-phase dissociation pathways of proteins/peptides are usually affected by the nature of the charge carrier and the sequence of amino acid residues. The effects of peptide structural parameters, including peptide composition, chain length and amide hydrogen, on the gas-phase dissociation of Cu(II)–model peptide complexes were explored in this study. Polyglycine peptides with flexible frames were used as probes to reduce the complexity of the system and illustrate the mechanism. Results revealed that the types of fragment ions generated in the electron capture dissociation (ECD) of Cu(II)-adducted peptides changed according to the basic amino acid residue composition. Charged or neutral tryptophan side-chain losses were observed in the collision-induced dissociation (CID) of Cu(II)–peptide complexes. Internal electron transfer between tryptophan and metal ion within the complex occurred during the CID reaction, leaving the charge-reduced Cu+ as a closed d-shell stable electron configuration. The choice of the reaction channel was then determined by the gas-phase basicity of the peptide. Amide hydrogen was critical in the formation of metalated b-/y-ions in the ECD process as determined through mutation of the backbone amide group. Increasing the chain length suppressed the ECD of Cu-metalated peptide species. Our results indicate that the structural parameters of peptides play important roles in the gas-phase dissociation processes of Cu–peptide complexes.
SolomonE.I.BaldwinM.J. and LoweryM.D., “Electronic structures of active sites in copper proteins: Contributions to reactivity”, Chem. Rev.92, 521 (1992). doi: http://dx.doi.org/10.1021/cr00012a003
WatsonH.M.VincentJ.B. and CassadyC.J., “Effects of transition metal ion coordination on the collision-induced dissociation of polyalanines”, J. Mass Spectrom.46, 1099 (1991). doi: http://dx.doi.org/10.1002/jms.1992
5.
WuZ.Fernandez-LimaF.A.PerezL.M. and RussellD.H., “A new copper containing MALDI matrix that yields high abundances of [peptide + Cu]+ ions”, J. Am. Soc. Mass Spectrom.20, 1263 (2009). doi: http://dx.doi.org/10.1016/j.jasms.2009.02.025
6.
HuP. and LooJ.A., “Gas-phase coordination properties of Zn2+, Cu2+, Ni2+, and Co2+ with histidine-containing peptides”, J. Am. Chem. Soc.117, 11314 (1995). doi: http://dx.doi.org/10.1021/ja00150a032
7.
Di MarcoV.B. and BombiG.G., “Electrospray mass spectrometry (ESI-MS) in the study of metal-ligand solution equilibria”, Mass Spectrom. Rev.25, 347 (2005). doi: http://dx.doi.org/10.1016/j.jasms.2009.02.025
8.
LooJ.A., “Probing protein-metal ion interactions by electrospray ionization mass spectrometry: Enolase and nucleocapsid protein”, Int. J. Mass Spectrom.204, 113 (2001). doi: http://dx.doi.org/10.1016/S1387-3806(00)00334-1
9.
ShiledS.J.BluhnB.K. and RussellD.H., “Fragmentation chemistry of [M + Cu]+ peptide ions containing an N-terminal arginine”, J. Am. Soc. Mass Spectrom.11, 626 (2000). doi: http://dx.doi.org/10.1016/S1044-0305(00)00128-8
10.
SeymourJ.L. and TurečekF., “Structure, energetics and reactivity of ternary complexes of amino acids with Cu(II) and 2,2′-bipyridine by density functional theory. A combination of radical-induced and spin-remote fragmentations”, J. Mass Spectrom.37, 533 (2002). doi: http://dx.doi.org/10.1016/j.jasms.2009.02.025
11.
VaisarT.GatlinC.L.RaoR.D.SeymourJ.L. and TurečekF., “Sequence information, distinction and quantitation of C-terminal leucine and isoleucine in ternary complexes of tripeptides with Cu(II) and 2,2′-bipyridine”, J. Mass Spectrom.36, 306 (2001). doi: http://dx.doi.org/10.1002/jms.135
12.
GatlinC.L.TurečekF. and VaisarT., “Determination of soluble Cu(I) and Cu(II) species in jet fuel by electrospray ionization mass spectrometry”, Anal. Chem.66, 3950 (1994). doi: http://dx.doi.org/10.1021/ac00094a016
13.
LavanantH.VirelizierH. and HoppilliardY., “Reduction of copper(II) complexes by electron capture in an electrospray ionization source”, J. Am. Soc. Mass Spectrom.9, 1217 (1998). doi: http://dx.doi.org/10.1016/S1044-0305(98)00100-7
14.
SiuC.K.KeY.GuoY.HopkinsonA.C. and SiuK.W.M., “Dissociations of copper(II)-containing complexes of aromatic amino acids: Radical cations of tryptophan, tyrosine, and phenylalanine”, Phys. Chem. Chem. Phys.10, 5908 (2008). doi: http://dx.doi.org/10.1039/B807692H
15.
ZubarevR.A.KelleherN.L. and McLaffertyF.W., “Electron capture dissociation of multiply charged protein cations: A nonergodic process”, J. Am. Chem. Soc.120, 3265 (1998). doi: http://dx.doi.org/10.1021/ja973478k
16.
IavaroneA.T.PaechK. and WilliamsE.R., “Effects of charge state and cationizing agent on the electron capture dissociation of a peptide”, Anal. Chem.76, 2231 (2004). doi: http://dx.doi.org/10.1021/ac035431p
17.
FungY.M.E.LiuH. and ChanT.W.D., “Electron capture dissociation of peptides metalated with alkaline-earth metal ions”, J. Am. Soc. Mass Spectrom.17, 757 (2006). doi: http://dx.doi.org/10.1016/j.jasms.2006.01.014
18.
KleinnijenhuisA.J.MihalcaR.HeerenR.M.A. and HeckA.J.R., “Atypical behavior in the electron capture induced dissociation of biologically relevant transition metal ion complexes of the peptide hormone oxytocin”, Int. J. Mass Spectrom.253, 217 (2006). doi: http://dx.doi.org/10.1016/j.ijms.2006.03.005
19.
LiuH. and HåkanssonK., “Divalent metal ion–peptide interactions probed by electron capture dissociation of trications”, J. Am. Soc. Mass Spectrom.17, 1731 (2006). doi: http://dx.doi.org/10.1016/j.jasms.2006.07.027
20.
YuriB.E.V.PalmbladM.DalleboutH. and HeerenR.M.A., “Electron capture dissociation of peptide hormone changes upon opening of the tocin ring and complexation with transition metal cation”, Rapid Commun. Mass Spectrom.23, 31 (2009). doi:_.
21.
FeketeováL.RyzhovV. and O'HairR.A.J., “Comparison of collision- versus electron-induced dissociation of Pt(II) ternary complexes of histidine- and methionine-containing peptides”, Rapid Commun. Mass Spectrom.23, 3133 (2009). doi: http://dx.doi.org/10.1002/rcm.4234
22.
TurečekF.JonesJ.W.HolmA.I.PanjaS.NielsenS.B. and HvelplundP., “Transition metals as electron traps. I. Structures, energetics, electron capture, and electron-transfer-induced dissociations of ternary copper–peptide complexes in the gas phase”, J. Mass Spectrom.44, 707 (2009). doi: http://dx.doi.org/10.1002/jms.1546
23.
AfonsoC.TabetJ.C.GiorgiG. and TurečekF., “Gasphase doubly charged complexes of cyclic peptides with copper in +1, +2 and +3 formal oxidation states: Formation, structures and electron capture dissociation”, J. Mass Spectrom.47, 208 (2012). doi: http://dx.doi.org/10.1002/jms.2956
24.
ChenX.FungY.M.E.ChanW.Y.K.WongP.S.YeungH.S. and ChanT.W.D., “Transition metal ions: Charge carriers that mediate the electron capture dissociation pathways of peptides”, J. Am. Soc. Mass Spectrom.22, 2232 (2011). doi: http://dx.doi.org/10.1007/s13361-011-0246-1
25.
ChenX.ChanW.Y.K.WongP.S.YeungH.S. and ChanT.W.D., “Formation of peptide radical cations (M+) in electron capture dissociation of peptides adducted with group IIB metal ions”, J. Am. Soc. Mass Spectrom.22, 233 (2011). doi: http://dx.doi.org/10.1007/s13361-010-0035-2
26.
DongJ. and VachetR.W., “Coordination sphere tuning of the electron transfer dissociation behavior of Cu(II)–peptide complexes”, J. Am. Soc. Mass Spectrom.23, 321 (2012). doi: http://dx.doi.org/10.1007/s13361-011-0299-1
27.
CerdaB.A. and WesdemiotisC., “The relative copper(I) ion affinities of amino acids in the gas phase”, J. Am. Chem. Soc.117, 9734 (1995). doi: http://dx.doi.org/10.1021/ja00143a017
28.
LauR.L.C.JiangJ.Z.NgD.K.P. and ChanT.W.D., “Fourier transform ion cyclotron resonance studies of lanthanide(III) porphyrin–phthalocyanine heteroleptic sandwich complexes by using electrospray ionization”, J. Am. Soc. Mass Spectrom.8, 161 (1997). doi: http://dx.doi.org/10.1016/S1044-0305(96)00173-0
29.
FongK.W.Y. and ChanT.W.D., “A novel nonmetallized tip for electrospray mass spectrometry at nanoliter flow rate”, J. Am. Soc. Mass Spectrom.10, 72 (1999). doi: http://dx.doi.org/10.1016/S1044-0305(98)00127-5
30.
ChanT.W.D. and IpW.H.H., “Optimization of experimental parameters for electron capture dissociation of peptides in a Fourier transform mass spectrometer”, J. Am. Soc. Mass Spectrom.13, 1396 (2002). doi: http://dx.doi.org/10.1016/S1044-0305(02)00703-1
31.
FungY.M.E. and ChanT.W.D., “Experimental and theoretical investigations of the loss of amino acid side chains in electron capture dissociation of model peptides”, J. Am. Soc. Mass Spectrom.16, 1523 (2005). doi: http://dx.doi.org/10.1016/j.jasms.2005.05.001
SigelH. and MartinR.B., “Coordinating properties of the amide bond. Stability and structure of metal ion complexes of peptides and related ligands”, Chem. Rev.82, 385 (1982). doi: http://dx.doi.org/10.1021/cr00050a003
34.
RimolaA.ConstantinoE.Rodriguez-SantiagoC. and SodupeM., “Binding properties of Cu+/2+−(glycyl)nglycine complexes (n = 1–3)”, J. Phys. Chem. A112, 3444 (2008). doi: http://dx.doi.org/10.1021/jp711189s
35.
HuP.SorensenC. and GrossM.L., “Influences of peptide side chains on the metal ion binding site in metal ion-cationized peptides: Participation of aromatic rings in metal chelation”, J. Am. Soc. Mass Spectrom.6, 1079 (1995). doi: http://dx.doi.org/10.1016/1044-0305(95)00549-8
36.
ChanW.Y.K. and ChanT.W.D., “Natural structural motifs that suppress peptide ion fragmentation after electron capture”, J. Am. Soc. Mass Spectrom.21, 1235 (2010). doi: http://dx.doi.org/10.1016/j.jasms.2010.03.034
37.
WongP.S.J.ChenX.DengL.WangZ.LiW.WongY.L.E. and ChanT.W.D., “Suppression of peptide ion dissociation under electron capture: Role of backbone amide hydrogen”, Rapid Commun. Mass Spectrom. (in press). doi: http://dx.doi.org/10.1002/rcm.7275
