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 #
5P50GM086145-05
Application #
8326708
Study Section
Special Emphasis Panel (ZGM1-PPBC-3 (CL))
Program Officer
Fabian, Miles
Project Start
2008-09-30
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$1,895,862
Indirect Cost
$489,077
Name
University of Chicago
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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
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
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
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
Xu, Yun; Hu, Changyu; Dai, Yang et al. (2014) On simplified global nonlinear function for fitness landscape: a case study of inverse protein folding. PLoS One 9:e104403
Yingzi Li; Naveed, Hammad; Jie Liang et al. (2014) Effects of mechanical properties on tumor invasion: insights from a cellular model. Conf Proc IEEE Eng Med Biol Soc 2014:6818-21
Jimenez-Morales, David; Adamian, Larisa; Shi, Dashuang et al. (2014) Lysine carboxylation: unveiling a spontaneous post-translational modification. Acta Crystallogr D Biol Crystallogr 70:48-57
Tian, Wei; Cao, Youfang; Ismael, Amber et al. (2014) Roles of regulated internalization in the polarization of cell surface receptors. Conf Proc IEEE Eng Med Biol Soc 2014:1166-9
Gürsoy, Gamze; Xu, Yun; Liang, Jie (2014) Computational predictions of structures of multichromosomes of budding yeast. Conf Proc IEEE Eng Med Biol Soc 2014:3945-8
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

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