title: Metastable atom-activated dissociation mass spectrometry: leucine/isoleucine differentiation and ring cleavage of proline residues.
abstract: Extensive backbone fragmentation resulting in a-, b-, c-, x-, y- and z-type ions is observed of singly and doubly charged peptide ions through their interaction with a high kinetic energy beam of argon or helium metastable atoms in a modified quadrupole ion trap mass spectrometer. The ability to determine phosphorylation-sites confirms the observation with previous reports and we report the new ability to distinguish between leucine and isoleucine residues and the ability to cleave two covalent bonds of the proline ring resulting in a-, b-, x-, y-, z- and w-type ions. The fragmentation spectra indicate that fragmentation occurs through nonergodic radical ion chemistry akin to electron capture dissociation (ECD), electron transfer dissociation (ETD) and electron ionization dissociation mechanisms. However, metastable atom-activated dissociation mass spectrometry demonstrates three apparent benefits to ECD and ETD: (1) the ability to fragment singly charged precursor ions, (2) the ability to fragment negatively charged ions and (3) the ability to cleave the proline ring that requires the cleavage of two covalent bonds. Helium metastable atoms generated more fragment ions than argon metastable atoms for both substance P and bradykinin regardless of the precursor ion charge state. Reaction times less than 250 ms and efficiencies approaching 5% are compatible with on-line fragmentation, as would be desirable for bottom-up proteomics applications.
authors.affiliation: Center for Intelligent Chemical Instrumentation, Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701-2979, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Cook
authors.forename: Olivier L
authors.initials: OL
authors.lastname: Collin
authors.forename: Glen P
authors.initials: GP
authors.lastname: Jackson
mesh_terms: D000804:Angiotensin II / Q000737:chemistry; D001920:Bradykinin / Q000737:chemistry; D002766:Cholecystokinin / Q000737:chemistry; D004151:Dipeptides / Q000737:chemistry; D005345:Fibrinopeptide B / Q000737:chemistry; D007532:Isoleucine / Q000032:analysis*; D007930:Leucine / Q000032:analysis*; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D010446:Peptide Fragments / Q000737:chemistry; D010750:Phosphoproteins / Q000737:chemistry*; D011392:Proline / Q000032:analysis*; D011506:Proteins / Q000737:chemistry*; D013373:Substance P / Q000737:chemistry
chemical_list: D004151:Dipeptides; D010446:Peptide Fragments; D010750:Phosphoproteins; D011506:Proteins; D007532:Isoleucine; C048641:cholecystokinin (10-20); D000804:Angiotensin II; D013373:Substance P; D005345:Fibrinopeptide B; D002766:Cholecystokinin; D011392:Proline; D007930:Leucine; D001920:Bradykinin