The main objective of our application to NIH is to establish the Chicago Tri-lnstitutional Center for Chemical Methods and Library Development (CTCMLD), which is designed to address the fundamental challenges of high-throughput organic synthesis and to provide major advances that will significantly facilitate the development of small-molecule libraries for broad biological screening. Our CTCMLD application is strongly supported by the three participating institutions and the Chicago Biomedical Consortium, which provided a $2 Million Lever Award to match the NIH funding. The CTCMLD will have several major goals listed below. Center Objective 1: Conduct four highly integrated projects that are designed to significantly facilitate the generation of chemical diversity and assembly of high-quality small-molecule libraries. The four proposed projects are: (a) practical synthesis of new nitrogen-based heterocyclic libraries (leaders: Scheldt and Gevorgyan);(b) multi-component assembly of polyketide libraries (leader: Yamamoto);(c) assembly of scaffold-unbiased small-molecule libraries (leader: Kozmin);and (d) development of tailored surfaces for new reaction development, miniaturized library synthesis and small-molecule immobilization (leader: Mrksich). The scientific projects will be carried out at the highest level, resulting in the development of an arsenal of new synthetic methods, which in turn will enable the generation of approximately 20,000 new compounds of 20 mg scale in highly efficient, parallel manner. Center Objective 2: Training the next generation of scientists, who will develop and arsenal of new methods and strategies for high-throughput organic synthesis. Center Objective 3: Establish core research facility for library synthesis, characterization and cheminformatics. The Core facility will have three highly integrated components: High-Throughput Synthesis Component located at the University of Chicago, Hit-to-Lead Development Resource located on Northwestern campus and Cheminformatics Core at the University of Illinois at Chicago. Objective 4: Provide broad outreach to the biology community enabling rapid and efficient screening of new compound libraries. In addition to providing new compounds for the NIH Roadmap Molecular Libraries Initiative, we will collaborate with three major high-throughput screening centers in Illinois, and many individual biology laboratories. The increased connectivity and synergy resulting from the work of the CTCMLD will represent a major advance in the Chicago area's capabilities and a paradigm shift in how the Chicago academic community will approach and solve problems at the interface of chemistry, biology and medicine.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM086145-04
Application #
8131018
Study Section
Special Emphasis Panel (ZGM1-PPBC-3 (CL))
Program Officer
Fabian, Miles
Project Start
2008-09-30
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
4
Fiscal Year
2011
Total Cost
$1,897,003
Indirect Cost
Name
University of Chicago
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Gursoy, Gamze; Terebus, Anna; Youfang Cao et al. (2016) Mechanisms of stochastic focusing and defocusing in biological reaction networks: insight from accurate chemical master equation (ACME) solutions. Conf Proc IEEE Eng Med Biol Soc 2016:1480-1483
Efimova, Elena V; Takahashi, Satoe; Shamsi, Noumaan A et al. (2016) Linking Cancer Metabolism to DNA Repair and Accelerated Senescence. Mol Cancer Res 14:173-84
Takeuchi, Toshifumi; Schumacker, Paul T; Kozmin, Sergey A (2015) Identification of fumarate hydratase inhibitors with nutrient-dependent cytotoxicity. J Am Chem Soc 137:564-7
Kachalo, Sëma; Naveed, Hammad; Cao, Youfang et al. (2015) Mechanical model of geometric cell and topological algorithm for cell dynamics from single-cell to formation of monolayered tissues with pattern. PLoS One 10:e0126484
Gürsoy, Gamze; Xu, Yun; Kenter, Amy L et al. (2014) Spatial confinement is a major determinant of the folding landscape of human chromosomes. Nucleic Acids Res 42:8223-30
Montgomery, Thomas D; Nibbs, Antoinette E; Zhu, Ye et al. (2014) Rapid access to spirocyclized indolenines via palladium-catalyzed cascade reactions of tryptamine derivatives and propargyl carbonate. Org Lett 16:3480-3
Tang, Ke; Zhang, Jinfeng; Liang, Jie (2014) Fast protein loop sampling and structure prediction using distance-guided sequential chain-growth Monte Carlo method. PLoS Comput Biol 10:e1003539
Brady, Patrick B; Oda, Susumu; Yamamoto, Hisashi (2014) Stereodivergent approach to the avermectins based on ""super silyl"" directed aldol reactions. Org Lett 16:3864-7
Sumaria, Chintan S; Türkmen, Yunus E; Rawal, Viresh H (2014) Non-precious metals catalyze formal [4 + 2] cycloaddition reactions of 1,2-diazines and siloxyalkynes under ambient conditions. Org Lett 16:3236-9
Terebus, Anna; Cao, Youfang; Liang, Jie (2014) Exact computation of probability landscape of stochastic networks of Single Input and Coupled Toggle Switch Modules. Conf Proc IEEE Eng Med Biol Soc 2014:5228-31

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