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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM104316-04
Application #
9302810
Study Section
Special Emphasis Panel (ZGM1-TWD-A)
Project Start
Project End
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
4
Fiscal Year
2017
Total Cost
$324,263
Indirect Cost
$117,219
Name
University of Delaware
Department
Type
Domestic Higher Education
DUNS #
059007500
City
Newark
State
DE
Country
United States
Zip Code
19716
Bush, Timothy S; Yap, Glenn P A; Chain, William J (2018) Transformation of N, N-Dimethylaniline N-Oxides into Diverse Tetrahydroquinoline Scaffolds via Formal Povarov Reactions. Org Lett 20:5406-5409
Liu, Jun; Cheng, Rujin; Wu, Haifan et al. (2018) Building and Breaking Bonds via a Compact S-Propargyl-Cysteine to Chemically Control Enzymes and Modify Proteins. Angew Chem Int Ed Engl 57:12702-12706
Macdougall, Laura J; Wiley, Katherine L; Kloxin, April M et al. (2018) Design of synthetic extracellular matrices for probing breast cancer cell growth using robust cyctocompatible nucleophilic thiol-yne addition chemistry. Biomaterials 178:435-447
LeValley, Paige J; Ovadia, Elisa M; Bresette, Christopher A et al. (2018) Design of functionalized cyclic peptides through orthogonal click reactions for cell culture and targeting applications. Chem Commun (Camb) 54:6923-6926
Drolen, Claire; Conklin, Eric; Hetterich, Stephen J et al. (2018) pH-Driven Mechanistic Switching from Electron Transfer to Energy Transfer between [Ru(bpy)3]2+ and Ferrocene Derivatives. J Am Chem Soc 140:10169-10178
Dicker, K T; Song, J; Moore, A C et al. (2018) Core-shell patterning of synthetic hydrogels via interfacial bioorthogonal chemistry for spatial control of stem cell behavior. Chem Sci 9:5394-5404
Sawicki, Lisa A; Choe, Leila H; Wiley, Katherine L et al. (2018) Isolation and Identification of Proteins Secreted by Cells Cultured within Synthetic Hydrogel-Based Matrices. ACS Biomater Sci Eng 4:836-845
Yu, Tiantian; Laird, Joanna R; Prescher, Jennifer A et al. (2018) Gaussia princeps luciferase: a bioluminescent substrate for oxidative protein folding. Protein Sci 27:1509-1517
Liu, Jun; Chen, Qingqing; Rozovsky, Sharon (2018) Selenocysteine-Mediated Expressed Protein Ligation of SELENOM. Methods Mol Biol 1661:265-283
Burch, Jason M; Mashayekh, Siavash; Wykoff, Dennis D et al. (2018) Bacterial Derived Carbohydrates Bind Cyr1 and Trigger Hyphal Growth in Candida albicans. ACS Infect Dis 4:53-58

Showing the most recent 10 out of 93 publications