The goal of this project is expand the chemical diversity available to the Molecular Library Probe Production Center Network (MLPCN) by providing the Molecular Libraries Small-Molecule Repository (MLSMR) a pilotscale library (PSL) of 10-25, novel or rare, structurally complex marine natural products per year. The compounds will be derived from marine macro-organisms in the HBOI Frozen Organism Repository including sponges, ascidians, cnidarians, and algae with an emphasis on organisms collected from less accessible deep-water marine environments. The primary focus of the project will be to provide compounds that are structurally new to science but in addition to these, rare natural products with unusual structures that are not currently available to the MLSMR will also be provided. All compounds provided will meet the MLSMR's criteria of 10 mg, >90% purity and solubility in either chloroform:methanol 9:1 or DMSO. HBOI has an exceptional collection of over 15,000 marine organisms that can be used in generation of the pilot-scale library with many of the organisms being unique to the HBOI collection. A recent project conducted by our research group to create a "Peak Library" of enriched fractions compatible with high throughput screening, has been highly successful in detecting unusual chemotypes in organisms which had not been chemically investigated in the past. The majority of the fractions in the Peak Library require only one additional purification step to provide pure materials and the scale of the initial fractionation (medium pressure liquid chromatography) leads readily to the isolation of larger quantities of materials. We have recently expanded the HBOI screening platform and have observed that many of the novel chemotypes found in the Peak Library affect unique biological targets and represent novel lead structures and excellent probes for studying biological processes. We will build upon the methods used to produce our Peak Library to create a unique pilot scale library of pure unusual natural products that expands the chemical diversity space currently available in the MLSMR.
The proposed research project will provide a unique pilot scale library of new and rare natural products to the Molecular Libraries Small Molecule Repository and expand the chemical diversity of the library. This will enhance the Molecular Roadmap's opportunities for meeting their goal of discovering new probes of biological mechanisms as well as compounds with unique biological activities relative to human health.
|Russell, Floyd; Harmody, Dedra; McCarthy, Peter J et al. (2013) Indolo[3,2-a]carbazoles from a deep-water sponge of the genus Asteropus. J Nat Prod 76:1989-92|