This application requests funding to acquire a Q-TOF mass spectrometer to replace the mass spectrometer component of an 18-year-old Bruker Esquire-LC/MS system, which is an essential part of the Shared Instrument Facility in the Department of Pharmaceutical Sciences at the University of Tennessee Health Science Center (UTHSC). The Bruker Esquire-LC/MS system has been well maintained and is the work horse supporting extensive small-molecular drug discovery and drug delivery programs at UTHSC in the areas of cancer, obesity, diabetes, radiation protection, radiation mitigation, bacteria inflection, and inflammation diseases. Several small-molecule drug candidates have been licensed for commercial development, including one currently in Phase III clinical trials. However, the age of the current mass spectrometer has resulted in more and more frequent breakdowns in recent years. Bruker officially stopped technical support for this type of instrument system in early 2010. Repair parts are scarce and have become very expensive. The proposed new Q-TOF mass spectrometer will replace the now unreliable mass spectrometer component of the Bruker Esquire-LC/MS system. This powerful new mass spectrometer will benefit more than 10 principal investigators supported by nine R01s, one RC2, one R33, three R21s, and other sources of support. The Q-TOF mass spectrometer will provide years of reliable accessibility, greater sensitivity in both MS and MS/MS modes, and the capability to obtain accurate mass for more efficient structure elucidation. This state-of-the-art instrument wil support drug discovery in preclinical development by using novel small molecules and their translation to innovative therapies for a variety of diseases. UTHSC is strongly committed to supporting biomedical research. The College of Pharmacy will provide $25,000 as a cost share for the purchase of the new instrument, fully support a staff scientist to maintain the Shared Instrument Facility, and assume all future maintenance and repair cost after the warranty period without charging user fees. An advisory committee will ensure effective utilization of the instrument and adequate access by the major users, other NIH-supported investigators, new investigators, and investigators with early-stage projects.

Public Health Relevance

The Q-TOF mass spectrometer requested will replace a technologically limited Esquire-LC/MS mass spectrometer that is nearly two decades old and will provide reliable and sophisticated support for 20 currently funded projects important to human health. These projects focus on small-molecule drug discovery and drug delivery in the areas of cancer, obesity, diabetes, radiation protection, radiation mitigation, bacteria inflection and inflammation diseases.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Biomedical Research Support Shared Instrumentation Grants (S10)
Project #
1S10OD010678-01
Application #
8246986
Study Section
Special Emphasis Panel (ZRG1-BCMB-P (30))
Program Officer
Birken, Steven
Project Start
2012-05-01
Project End
2013-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
1
Fiscal Year
2012
Total Cost
$325,000
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Slominski, Andrzej T; Kim, Tae-Kang; Hobrath, Judith V et al. (2016) Endogenously produced nonclassical vitamin D hydroxy-metabolites act as "biased" agonists on VDR and inverse agonists on RORα and RORγ. J Steroid Biochem Mol Biol :
Lin, Zongtao; Marepally, Srinivasa R; Kim, Tae-Kang et al. (2016) Design, Synthesis and Biological Activities of Novel Gemini 20S-Hydroxyvitamin D3 Analogs. Anticancer Res 36:877-86
Slominski, Andrzej T; Kim, Tae-Kang; Li, Wei et al. (2015) Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland. Sci Rep 5:14875
Lin, Zongtao; Marepally, Srinivasa Reddy; Ma, Dejian et al. (2015) Chemical Synthesis and Biological Activities of 20S,24S/R-Dihydroxyvitamin D3 Epimers and Their 1α-Hydroxyl Derivatives. J Med Chem 58:7881-7
Slominski, Andrzej T; Janjetovic, Zorica; Kim, Tae-Kang et al. (2015) Novel non-calcemic secosteroids that are produced by human epidermal keratinocytes protect against solar radiation. J Steroid Biochem Mol Biol 148:52-63
Wang, Qinghui; Lin, Zongtao; Kim, Tae-Kang et al. (2015) Total synthesis of biologically active 20S-hydroxyvitamin D3. Steroids 104:153-62
Kim, Tae-Kang; Lin, Zongtao; Tidwell, William J et al. (2015) Melatonin and its metabolites accumulate in the human epidermis in vivo and inhibit proliferation and tyrosinase activity in epidermal melanocytes in vitro. Mol Cell Endocrinol 404:1-8
Tieu, Elaine W; Li, Wei; Chen, Jianjun et al. (2015) Metabolism of 20-hydroxyvitamin D3 and 20,23-dihydroxyvitamin D3 by rat and human CYP24A1. J Steroid Biochem Mol Biol 149:153-65
Kim, Tae-Kang; Lin, Zongtao; Li, Wei et al. (2015) N1-Acetyl-5-Methoxykynuramine (AMK) is produced in the human epidermis and shows antiproliferative effects. Endocrinology 156:1630-6
Xiao, Min; Wang, Jin; Lin, Zongtao et al. (2015) Design, Synthesis and Structure-Activity Relationship Studies of Novel Survivin Inhibitors with Potent Anti-Proliferative Properties. PLoS One 10:e0129807

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