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.
|Stierle, Andrea A; Stierle, Donald B; Decato, Daniel et al. (2017) The Berkeleylactones, Antibiotic Macrolides from Fungal Coculture. J Nat Prod 80:1150-1160|
|Brindisi, Margherita; Maramai, Samuele; Gemma, Sandra et al. (2016) Development and Pharmacological Characterization of Selective Blockers of 2-Arachidonoyl Glycerol Degradation with Efficacy in Rodent Models of Multiple Sclerosis and Pain. J Med Chem 59:2612-32|
|Diaz, Philippe; Huang, Weize; Keyari, Charles M et al. (2016) Development and Characterization of Novel and Selective Inhibitors of Cytochrome P450 CYP26A1, the Human Liver Retinoic Acid Hydroxylase. J Med Chem 59:2579-95|
|Stierle, Andrea A; Stierle, Donald B; Girtsman, Teri et al. (2015) Azaphilones from an Acid Mine Extremophile Strain of a Pleurostomophora sp. J Nat Prod 78:2917-23|
|Weaver, Matthew J; Kearns, Alison K; Stump, Sascha et al. (2015) AIMing towards improved antitumor efficacy. Bioorg Med Chem Lett 25:1765-1770|
|Bladen, Chris; McDaniel, Steven W; Gadotti, Vinicius M et al. (2015) Characterization of novel cannabinoid based T-type calcium channel blockers with analgesic effects. ACS Chem Neurosci 6:277-87|
|Stierle, Andrea A; Stierle, Donald B (2014) Bioactive secondary metabolites from acid mine waste extremophiles. Nat Prod Commun 9:1037-44|
|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|
|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|
Showing the most recent 10 out of 43 publications