To provide academic researchers with high-quality compound collections for biological screening, the National Institute of General Medical Sciences established the Chemical Methodologies and Library Development (CMLD) Network and charged it with developing new ways of creating libraries and providing them to the SMR. The CMLD network was maintained under a R41 funding mechanism and has been discontinued, making it eligible for consideration as a legacy resource under the present program announcement. As part of the CMLD network, the University of Kansas CMLD center was responsible for developing numerous chemical methods and for providing >7000 compounds to the SMR. Most excitingly, numerous KU CMLD center compounds have been identified as hits in diverse screens, with a few progressing to full-blown development efforts currently underway. The NIH plans to maintain the SMR for the foreseeable future, with new screens being enabled by currently active, project-specific R01 awards (PAR-12-058), meaning that new hits will continue to be identified. However, the ability of researchers to have continued access to non-commercial compounds, which constitute a valuable and unique asset of the repository, is threatened by diminishing supplies of these compounds, many of which have been depleted. This threat is particularly acute with respect to pure samples (generally powders) that are essential for validation efforts following the initial screen. We propose to address these concerns through the present program. Our near-term goal is to supply scientists who have uncovered screening hits in the SMR with structurally validated quantitatively quality-controlled samples of the hit of interest as well as chemically similar analogs for validation efforts. This wll require a sustained effort in scientific outreach to maximize the potential client base for these activities as well as technical maintenance of our synthetic and compound purification/management capabilities Our long-term goal is to transform our library synthesis and hit validation activities into a sustainable effort that will eventually be supported by cost recovry from project-specific research grants and charge-backs to clients.
Discovery of new compounds for biomedical research and drug discovery often begins with testing numerous collections of novel chemical compounds, called libraries, in a variety of biological assays. This program will ensure that a particularly valuable library, the University of Kansas Chemical Methodologies and Library Development collection, will continue to be made available to researchers for validation of promising results obtained in such screens. To do this, compounds of interest will be re-prepared and sent to collaborators as requested.
|Klaus, Jennifer R; Deay, Jacqueline; Neuenswander, Benjamin et al. (2018) Malleilactone Is a Burkholderia pseudomallei Virulence Factor Regulated by Antibiotics and Quorum Sensing. J Bacteriol 200:|
|Sherwood, Alexander M; Prisinzano, Thomas E (2018) Novel psychotherapeutics - a cautiously optimistic focus on Hallucinogens. Expert Rev Clin Pharmacol 11:1-3|
|Sherwood, Alexander M; Williamson, Samuel E; Johnson, Stephanie N et al. (2018) Scalable Regioselective and Stereoselective Synthesis of Functionalized (E)-4-Iodobut-3-en-1-ols: Gram-Scale Total Synthesis of Fungal Decanolides and Derivatives. J Org Chem 83:980-992|
|Evans, Kara C; Benomar, Saida; Camuy-Vélez, Lennel A et al. (2018) Quorum-sensing control of antibiotic resistance stabilizes cooperation in Chromobacterium violaceum. ISME J 12:1263-1272|
|Sherwood, Alexander M; Williamson, Samuel E; Crowley, Rachel S et al. (2017) Modular Approach to pseudo-Neoclerodanes as Designer ?-Opioid Ligands. Org Lett 19:5414-5417|
|Sherwood, Alexander M; Crowley, Rachel Saylor; Paton, Kelly F et al. (2017) Addressing Structural Flexibility at the A-Ring on Salvinorin A: Discovery of a Potent Kappa-Opioid Agonist with Enhanced Metabolic Stability. J Med Chem 60:3866-3878|
|Yilmaz, Anil; Crowley, Rachel Saylor; Sherwood, Alexander M et al. (2017) Semisynthesis and Kappa-Opioid Receptor Activity of Derivatives of Columbin, a Furanolactone Diterpene. J Nat Prod 80:2094-2100|
|Crowley, Rachel Saylor; Riley, Andrew P; Sherwood, Alexander M et al. (2016) Synthetic Studies of Neoclerodane Diterpenes from Salvia divinorum: Identification of a Potent and Centrally Acting ? Opioid Analgesic with Reduced Abuse Liability. J Med Chem 59:11027-11038|
|McLeod, Michael C; Aubé, Jeffrey (2016) Efficient access to sp(3)-rich tricyclic amine scaffolds through Diels-Alder reactions of azide-containing silyloxydienes. Tetrahedron 72:3766-3774|