@article {2437,
	title = {Identification of Nitroxyl-induced Modifications in Human Platelet Proteins Using a Novel Mass Spectrometric Detection Method},
	journal = {Molecular \& Cellular Proteomics},
	volume = {8},
	number = {5},
	year = {2009},
	note = {ISI Document Delivery No.: 446JCTimes Cited: 5Cited Reference Count: 67Hoffman, Michael D. Walsh, Geraldine M. Rogalski, Jason C. Kast, Juergen},
	month = {May},
	pages = {887-903},
	type = {Article},
	abstract = {Nitroxyl (HNO) exhibits many important pharmacological effects, including inhibition of platelet aggregation, and the HNO donor Angeli{\textquoteright}s salt has been proposed as a potential therapeutic agent in the treatment of many diseases including heart failure and alcoholism. Despite this, little is known about the mechanism of action of HNO, and its effects are rarely linked to specific protein targets of HNO or to the actual chemical changes that proteins undergo when in contact with HNO. Here we study the presumed major molecular target of HNO within the body: protein thiols. Cysteine-containing tryptic peptides were reacted with HNO, generating the sulfinamide modification and, to a lesser extent, disulfide linkages with no other long lived intermediates or side products. The sulfinamide modification was subjected to a comprehensive tandem mass spectrometric analysis including MS/MS by CID and electron capture dissociation as well as an MS3 analysis. These studies revealed a characteristic neutral loss of HS(O)NH2 (65 Da) that is liberated from the modified cysteine upon CID and can be monitored by mass spectrometry. Upon storage, partial conversion of the sulfinamide to sulfinic acid was observed, leading to coinciding neutral losses of 65 and 66 Da (HS(O)OH). Validation of the method was conducted using a targeted study of nitroxylated glyceraldehyde-3-phosphate dehydrogenase extracted from Angeli{\textquoteright}s salt-treated human platelets. In these ex vivo experiments, the sample preparation process resulted in complete conversion of sulfinamide to sulfinic acid, making this the sole subject of further ex vivo studies. A global proteomics analysis to discover platelet proteins that carry nitroxyl-induced modifications and a mass spectrometric HNO dose-response analysis of the modified proteins were conducted to gain insight into the specificity and selectivity of this modification. These methods identified 10 proteins that are modified dose dependently in response to HNO, whose functions range from metabolism and cytoskeletal rearrangement to signal transduction, providing for the first time a possible mechanistic link between HNO-induced modification and the physiological effects of HNO donors in platelets. Molecular \& Cellular Proteomics 8: 887-903, 2009.},
	keywords = {ACTIVATION, ALDEHYDE, ALZHEIMERS-DISEASE, BIOLOGICAL-ACTIVITY, DEHYDROGENASE, DETERRENT AGENT CYANAMIDE, INTEGRIN, NITRIC-OXIDE, NITROGEN-OXIDE, NMDA RECEPTOR, S-NITROSYLATION, SUCCINIMIDE FORMATION},
	isbn = {1535-9476},
	url = {<Go to ISI>://000266116900002},
	author = {Hoffman, M. D. and Walsh, G. M. and Rogalski, J. C. and Kast, J.}
}
@article {2103,
	title = {Current approaches for global post-translational modification discovery and mass spectrometric analysis},
	journal = {Analytica Chimica Acta},
	volume = {627},
	number = {1},
	year = {2008},
	note = {ISI Document Delivery No.: 358IYTimes Cited: 13Cited Reference Count: 77Hoffman, Michael D. Sniatynski, Matthew J. Kast, JuergenSp. Iss. SI},
	month = {Oct},
	pages = {50-61},
	type = {Review},
	abstract = {More and more attention is being focused on the analysis of post-translational modifications (PTMs) on proteins as researchers are continually learning how essential they are for proper cellular function. As there are hundreds of different types of known PTMs, traditional methods of modification analysis are incapable of comprehensively monitoring for post-translational modifications, a task which is a necessity for truly understanding a cell{\textquoteright}s biology. This review highlights recent developments in novel multiplexed methods of PTM analysis including: fluorescent stain and immuno-based methods, hardware-based mass spectrometric methods and computational-based mass spectrometric methods. Many of these techniques show great promise and will likely be a valuable resource for the biological community. (C) 2008 Elsevier B.V. All rights reserved.},
	keywords = {computational, glycosylation, IDENTIFICATION, IONIZATION, marker ion, MASS SPECTROMETRY, MODIFIED PEPTIDES, neutral loss, post-translational modifications, protein array, PROTEIN-PHOSPHORYLATION, PROTEOMIC ANALYSIS, S-NITROSYLATION, SEQUENCES, SIGNALING NETWORKS, SPECTRA},
	isbn = {0003-2670},
	url = {<Go to ISI>://000259911600005},
	author = {Hoffman, M. D. and Sniatynski, M. J. and Kast, J.}
}
