This application will establish a Core Laboratory in Neuromolecular Production (CLNP) that provides neuroscience researchers with customized small molecule tools, consultation, resources and support to assist and advance their investigations. The Core Laboratory in Neuromolecular Production will establish and maintain essential chemistry support for neuroscience investigators including the preparation, optimization, purification and/or separation of small molecule reagents, probes and/or targets that are focused on neurotransmitter-based structures. The CLNP will undertake the synthesis of bioactive ligands, cross-linkers, isotope enriched structures, peptides, structure and imagine probes, protein-tags and bioconjugates, library development (target- and diversity-oriented syntheses), and other molecular ensembles. The CLNP will be achieved with the addition of new space, creation of a dedicated CLNP lab and program suite, a teamwork-oriented administration, workgroup-based problem solving, integration with existing cores, and the hiring of highly trained chemistry personnel to design, maintain, and execute the requested projects and services. The long-range objectives are to advance the CLNP as a dependable and sustainable service and resource to neuroscience investigators that introduces small molecule archives (warehouse) and chemoinformatic databases capable of generating new research avenues.
The specific aims of this application are to: (1) design, build, and launch a Core Laboratory in Neuromolecular Production, (2) provide neuroscience investigators with customized neurotransmitter-based, ligands, probes, bioconjugates and resources to aid and enhance their existing, pending and planned NINDS-based research programs, (3) develop workgroups that promote collaborations and multi-laboratory problem solving using neurotransmitter-based ligands, probes and bioconjugates, and (4) create, manage and disseminate for public use a cheminformatic database and repository of neurotransmitter-based ligands, probes and bioconjugates. Public Health Relevance: This application seeks to develop a facility that provides customized small molecules to neuroscientists. Small molecule development is an essential first step toward developing drugs that may be helpful in battling CNS diseases.

Public Health Relevance

This application seeks to develop a facility that provides customized small molecules to neuroscientists. Small molecule development is an essential first step toward developing drugs that may be helpful in battling CNS diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Center Core Grants (P30)
Project #
5P30NS055022-05
Application #
8388006
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
2014-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
5
Fiscal Year
2013
Total Cost
$211,295
Indirect Cost
$61,970
Name
University of Montana
Department
Type
DUNS #
010379790
City
Missoula
State
MT
Country
United States
Zip Code
59812
James, Shelly L; Ahmed, S Kaleem; Murphy, Stephanie et al. (2014) A novel fluorine-18 ?-fluoroethoxy organophosphate positron emission tomography imaging tracer targeted to central nervous system acetylcholinesterase. ACS Chem Neurosci 5:519-24
Newell, J L; Keyari, C M; McDaniel, S W et al. (2014) Novel di-aryl-substituted isoxazoles act as noncompetitive inhibitors of the system Xc(-) cystine/glutamate exchanger. Neurochem Int 73:132-8
Carrigan, Christina N; Patel, Sarjubhai A; Cox, Holly D et al. (2014) The development of benzo- and naphtho-fused quinoline-2,4-dicarboxylic acids as vesicular glutamate transporter (VGLUT) inhibitors reveals a possible role for neuroactive steroids. Bioorg Med Chem Lett 24:850-4
Stierle, Andrea A; Stierle, Donald B; Mitman, Grant G et al. (2014) Phomopsolides and related compounds from the alga-associated fungus, Penicillium clavigerum. Nat Prod Commun 9:87-90
Prins, John M; Chao, Chih-Kai; Jacobson, Saskia M et al. (2014) Oxidative stress resulting from exposure of a human salivary gland cells to paraoxon: an in vitro model for organophosphate oral exposure. Toxicol In Vitro 28:715-21
Stierle, Andrea A; Stierle, Donald B (2014) Bioactive secondary metabolites from acid mine waste extremophiles. Nat Prod Commun 9:1037-44
Gadotti, Vinicius M; You, Haitao; Petrov, Ravil R et al. (2013) Analgesic effect of a mixed T-type channel inhibitor/CB2 receptor agonist. Mol Pain 9:32
Petrov, Ravil R; Knight, Lindsay; Chen, Shao-Rui et al. (2013) Mastering tricyclic ring systems for desirable functional cannabinoid activity. Eur J Med Chem 69:881-907
Matti, Afnan A; Mirzaei, Joseph; Rudolph, John et al. (2013) Microwave accelerated synthesis of isoxazole hydrazide inhibitors of the system xc- transporter: Initial homology model. Bioorg Med Chem Lett 23:5931-5
Astruc-Diaz, Fanny; McDaniel, Steven W; Xu, Jijun J et al. (2013) In vivo efficacy of enabling formulations based on hydroxypropyl-?-cyclodextrins, micellar preparation, and liposomes for the lipophilic cannabinoid CB2 agonist, MDA7. J Pharm Sci 102:352-64

Showing the most recent 10 out of 32 publications