The specific aims are: A. To develop novel methods using laser desorption extended-range mass spectrometry to qualitatively (and subsequently, semi-quantitatively or quantitatively) determine the presence of multiple neuropeptides derived from a single gene product (e.g. prodynorphin and processed dynorphin A peptides; proenkephalin and processed enkephalin peptides; proopiomelanocortin (POMC) parent peptide and multiple peptides derived from POMC, adrenocorticotropin hormone (ACTH), ?-endorphin, ?-melanocyte-stimulating hormone (MSH) and ?-MSH). B. To use these novel techniques (alone or in combination with HPLC and/or RIA) for the simultaneous qualitative and/or quantitative analysis of opioid peptides and other neuropeptides related to the endogenous opioid system (e.g. Corticotropin releasing factor (CRF), cholecystokinin (CCK), substance P and their processed peptides). C. To use these techniques in studies of the effects of alterations in levels of activity of neurotransmitters on the processing of endogenous opioids (e.g. the effects of altered levels of dopamine on dynorphin processing). D. To use these techniques to study the effects of drugs of abuse and potential treatment agents on opioid peptide processing and degradation (e.g. cocaine, morphine and ethanol effects; methadone, nalmefene and fluoxetine effects). Papers describing this work were published (see below) or are in press. J. Yu, B.T. Chait, L.Toll and M.J. Kreek """"""""Noniceptin in vitro Biotransformation in Human Blood"""""""" Peptides 17 (1996) 873-876. 1.5 J. Yu, E.R. Butelman, J.H Woods, B.T. Chait, M. J. Kreek """"""""In vitro Biotransformation of Dynorphin A (1-17) is Similar in Human and Rhesus Monkey Blood as studied by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry"""""""" J. Pharmacology and Experimental Therapeutics, 279 (1996) 507 - 514. J. Z. Chou, B.T. Chait, R.Wang, M.J. Kreek """"""""Differential Biotransformation of Dynorphin A (1-17) and Dynorphin A (1-13) Peptides in Human Blood, ex vivo"""""""". Peptides. (Tarrytown, NY) 17 (1996) 983-990. J. Yu, E.R. Butelman, J.H. Woods, B.T. Chait, M.J. Kreek """"""""Dynorphin A(1-8) Analog, E-2078, is stable in Human and Rhesus Monkey Blood"""""""" J. Pharm. Experimental Therapeutics 280 (1997) 1147-1151.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000862-28
Application #
6417124
Study Section
Project Start
2000-12-01
Project End
2002-02-28
Budget Start
Budget End
Support Year
28
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Rockefeller University
Department
Type
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Manning, Lois R; Popowicz, Anthony M; Padovan, Julio C et al. (2017) Gel filtration of dilute human embryonic hemoglobins reveals basis for their increased oxygen binding. Anal Biochem 519:38-41
Boice, Michael; Salloum, Darin; Mourcin, Frederic et al. (2016) Loss of the HVEM Tumor Suppressor in Lymphoma and Restoration by Modified CAR-T Cells. Cell 167:405-418.e13
Chait, Brian T; Cadene, Martine; Olinares, Paul Dominic et al. (2016) Revealing Higher Order Protein Structure Using Mass Spectrometry. J Am Soc Mass Spectrom 27:952-65
Krutchinsky, Andrew N; Padovan, Júlio C; Cohen, Herbert et al. (2015) Maximizing ion transmission from atmospheric pressure into the vacuum of mass spectrometers with a novel electrospray interface. J Am Soc Mass Spectrom 26:649-58
Mast, Fred D; Rachubinski, Richard A; Aitchison, John D (2015) Signaling dynamics and peroxisomes. Curr Opin Cell Biol 35:131-6
Krutchinsky, Andrew N; Padovan, Júlio C; Cohen, Herbert et al. (2015) Optimizing electrospray interfaces using slowly diverging conical duct (ConDuct) electrodes. J Am Soc Mass Spectrom 26:659-67
Oricchio, Elisa; Papapetrou, Eirini P; Lafaille, Fabien et al. (2014) A cell engineering strategy to enhance the safety of stem cell therapies. Cell Rep 8:1677-1685
Zhong, Yu; Morris, Deanna H; Jin, Lin et al. (2014) Nrbf2 protein suppresses autophagy by modulating Atg14L protein-containing Beclin 1-Vps34 complex architecture and reducing intracellular phosphatidylinositol-3 phosphate levels. J Biol Chem 289:26021-37
Indiani, Chiara; O'Donnell, Mike (2013) A proposal: Source of single strand DNA that elicits the SOS response. Front Biosci (Landmark Ed) 18:312-23
Di Virgilio, Michela; Callen, Elsa; Yamane, Arito et al. (2013) Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching. Science 339:711-5

Showing the most recent 10 out of 67 publications