The ability to characterize entire classes of proteins based on activity would greatly accelerate both the assignment of protein function in the genome era and the identification of new biomarl

Public Health Relevance

A large fraction of human enzymes remain uncharacterized in terms of their function in health and disease. We have developed advanced chemical technologies to functionally characterize enzymes directly in native biological systems. The goal of this application is to further develop and apply these technologies to identify enzymes that play important roles in cancer, which may serve as valuable new biomarkers and therapeutic targets.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37CA087660-15
Application #
8803892
Study Section
Special Emphasis Panel (NSS)
Program Officer
Fu, Yali
Project Start
2014-03-01
Project End
2019-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
15
Fiscal Year
2014
Total Cost
$294,818
Indirect Cost
$139,241
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Backus, Keriann M; Correia, Bruno E; Lum, Kenneth M et al. (2016) Proteome-wide covalent ligand discovery in native biological systems. Nature 534:570-4
Blewett, Megan M; Xie, Jiji; Zaro, Balyn W et al. (2016) Chemical proteomic map of dimethyl fumarate-sensitive cysteines in primary human T cells. Sci Signal 9:rs10
Chen, Wentao; Dong, Jiajia; Plate, Lars et al. (2016) Arylfluorosulfates Inactivate Intracellular Lipid Binding Protein(s) through Chemoselective SuFEx Reaction with a Binding Site Tyr Residue. J Am Chem Soc 138:7353-64
Chang, Jae Won; Zuhl, Andrea M; Speers, Anna E et al. (2015) Selective inhibitor of platelet-activating factor acetylhydrolases 1b2 and 1b3 that impairs cancer cell survival. ACS Chem Biol 10:925-32
Kohnz, Rebecca A; Mulvihill, Melinda M; Chang, Jae Won et al. (2015) Activity-Based Protein Profiling of Oncogene-Driven Changes in Metabolism Reveals Broad Dysregulation of PAFAH1B2 and 1B3 in Cancer. ACS Chem Biol 10:1624-30
Cognetta 3rd, Armand B; Niphakis, Micah J; Lee, Hyeon-Cheol et al. (2015) Selective N-Hydroxyhydantoin Carbamate Inhibitors of Mammalian Serine Hydrolases. Chem Biol 22:928-37
Wang, Chu; Weerapana, Eranthie; Blewett, Megan M et al. (2014) A chemoproteomic platform to quantitatively map targets of lipid-derived electrophiles. Nat Methods 11:79-85
Niphakis, Micah J; Cravatt, Benjamin F (2014) Enzyme inhibitor discovery by activity-based protein profiling. Annu Rev Biochem 83:341-77
Dix, Melissa M; Simon, Gabriel M; Cravatt, Benjamin F (2014) Global identification of caspase substrates using PROTOMAP (protein topography and migration analysis platform). Methods Mol Biol 1133:61-70
Lanning, Bryan R; Whitby, Landon R; Dix, Melissa M et al. (2014) A road map to evaluate the proteome-wide selectivity of covalent kinase inhibitors. Nat Chem Biol 10:760-7

Showing the most recent 10 out of 63 publications