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.
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