The proposed COBRE will focus a diverse group of scientists on a central mission?to enable discovery of new therapeutic leads and molecules that probe the function of biological targets. This COBRE represents a new scientific direction for the University of Delaware (UD), and researchers in the center will develop methods for creating, screening and analyzing probe molecules and their biological targets on a scale that cannot be supported by existing core instrumentation. Accordingly, a research core of considerable infrastructure will be created in order to promote the success ofthe center. This COBRE will establish a Screening, Analysis and Synthesis (SAS) Research Core that facilitates high throughput synthesis and rapid purification of molecular libraries. The SAS core will enable printing libraries of immunostimulatory molecules and the creation of ultra-sensitive detection methods for chip-based binding assays. The SAS will house instrumentation for the high throughput assessment of cell response to small molecules and will facilitate the creation of the first in vitro assay for Huntington's disease. A plan for the oversight and maintenance ofthe SAS core is outlined. This COBRE will also enable the discovery of computational methods that are capable of permitting lead structures to be predicted and optimized in a rational manner. To facilitate the intensive computation that will be needed, we will expand an existing IDeA-funded computational cluster with the addition of 504 compute cores. The cluster is designed to be suited for highly parallel molecular dynamics, density functional theory calculations, and high throughput virtual screening. A plan for oversight and maintenance ofthe computational core is outlined.
The medicinal field is currently limited by the ability to discover new classes of molecules that can probe and treat human disease. The proposed work will have impact on discovery of molecules that can be used to study and treat a number of diseases, including cancer, Crohn's disease, Huntington's disease, Alzheimer's disease, and Creutzfeldt-Jakob disease.
|Cinderella, Andrew P; Vulovic, Bojan; Watson, Donald A (2017) Palladium-Catalyzed Cross-Coupling of Silyl Electrophiles with Alkylzinc Halides: A Silyl-Negishi Reaction. J Am Chem Soc 139:7741-7744|
|Cobb, Kelsey M; Rabb-Lynch, Javon M; Hoerrner, Megan E et al. (2017) Stereospecific, Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling of Allylic Pivalates To Deliver Quaternary Stereocenters. Org Lett 19:4355-4358|
|Lambert, William D; Scinto, Samuel L; Dmitrenko, Olga et al. (2017) Computationally guided discovery of a reactive, hydrophilic trans-5-oxocene dienophile for bioorthogonal labeling. Org Biomol Chem 15:6640-6644|
|Vulovic, Bojan; Watson, Donald A (2017) Heck-like Reactions Involving Heteroatomic Electrophiles. European J Org Chem 2017:4996-5009|
|Guo, Chen; Kim, Heejae; Ovadia, Elisa M et al. (2017) Bio-orthogonal conjugation and enzymatically triggered release of proteins within multi-layered hydrogels. Acta Biomater 56:80-90|
|Rezazadeh, Sina; Devannah, Vijayarajan; Watson, Donald A (2017) Nickel-Catalyzed C-Alkylation of Nitroalkanes with Unactivated Alkyl Iodides. J Am Chem Soc 139:8110-8113|
|Urello, Morgan A; Kiick, Kristi L; Sullivan, Millicent O (2017) ECM turnover-stimulated gene delivery through collagen-mimetic peptide-plasmid integration in collagen. Acta Biomater 62:167-178|
|Wolfe, Aaron J; Si, Wei; Zhang, Zhengqi et al. (2017) Quantification of Membrane Protein-Detergent Complex Interactions. J Phys Chem B 121:10228-10241|
|Basch, Corey H; Liao, Jennie; Xu, Jianyu et al. (2017) Harnessing Alkyl Amines as Electrophiles for Nickel-Catalyzed Cross Couplings via C-N Bond Activation. J Am Chem Soc 139:5313-5316|
|Gietter-Burch, Amber A S; Devannah, Vijayarajan; Watson, Donald A (2017) Trifluoromethylation of Secondary Nitroalkanes. Org Lett 19:2957-2960|
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