Kodadek, Thomas - The Scripps Research Institute

研究领域

The Kodadek laboratory works in the general area of chemical biology with an emphasis on translational research. The laboratory employs a broad spectrum of techniques that span organic chemistry to molecular genetics. Several projects focus on novel methods to monitor and manipulate the immune system. One goal of these efforts is to discover effective and early diagnostic tests for a variety of disease states, including cancers, autoimmune diseases and neurodegenerative conditions. Another is to identify compounds that act as “antigen surrogates” in that they have the ability to recognize the antigen-binding sites of antibodies and T cell receptors. These compounds are being developed as potential therapeutic agents to block autoimmune responses selectively without interfering with the healthy functioning of the immune system. Another major project area is to develop better libraries and more efficient screening technologies for the discovery of protein ligands and bioactive compounds. For example, new classes of oligomeric, bio-inspired compounds are being created and new methods that will allow the rapid screening of tens of millions of compounds at a time are being developed. Finally, the Kodadek laboratory is interested in understanding the biology of many of the systems that are being targeted pharmacologically. For example, one project aims to understand the biochemical mechanisms underlying orexin signaling, which triggers wakefulness in mammals. Another seeks to better understand the role of the proteasome in transcriptional regulation. Diseases that are under investigation include Alzheimer's disease, Neuromyelitis Optica, Multiple Sclerosis, Pancreatic Cancer, Narcolepsy, Chronic Lymphoid Leukemia and various other cancers.

近期论文

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Doran, T.M., Simanski, S. and Kodadek, T. (2014) “Discovery of native autoantigens via antigen surrogate technology: Application to type 1 diabetes” ACS Chem. Biol. 9, In press. Gao, Y. and Kodadek, T. (2014) “Direct comparison of linear and macrocyclic compounds as a source of protein ligands” ACS Comb. Sci. 9, In press. Gao, Y., Amar, S., Pahwa, S., Fields, G. and Kodadek, T. (2014) “Rapid lead discovery through iterative screening of one bead one compound libraries” ACS Comb. Sci. 9, In press. Cravatt, B.F. and Kodadek, T. (2014) “Methods to monitor and manipulate biological systems: recent advances in “omics” Curr. Opin. Chem. Biol. 24, In press. Sarma BK, Liu X, Wu H, Gao Y, Kodadek T. (2014) Solid phase synthesis of 1,3,4-oxadiazin-5 (6R)-one and 1,3,4-oxadiazol-2-one scaffolds from acyl hydrazides. Org Biomol Chem. 12, 59-63. Sarkar, M., Liu, Y., Morimoto, J., Peng, H., Aquino, C., Rader, C., Chiorazzi, N. and Kodadek, T. (2014) “Recognition of antigen-specific B cell receptors from chronic lymphocytic leukemia patients by synthetic “antigen surrogates” Chem & Biol. 21, In press. Morimoto J, Sarkar M, Kenrick S, Kodadek T. (2014) Dextran as a Generally Applicable Multivalent Scaffold for Improving Immunoglobulin-Binding Affinities of Peptide and Peptidomimetic Ligands. Bioconjug Chem. 25, 1479-1491. Kodadek T. (2014) Chemical tools to monitor and manipulate the adaptive immune system. Chem Biol. 21(9):1066-74. Review. Suwal S, Kodadek T. (2014) Solid-phase synthesis of peptoid-like oligomers containing diverse diketopiperazine units. Org Biomol Chem. 12(31):5831-4. Doran TM, Gao Y, Mendes K, Dean S, Simanski S, Kodadek T. (2014) Utility of redundant combinatorial libraries in distinguishing high and low quality screening hits. ACS Comb Sci. 16(6):259-70. Vanderstichele H, Kodadek T. (2014). Roadblocks for integration of novel biomarker concepts into clinical routine: the peptoid approach. Alzheimers Res Ther. 6(2):23. Review. Gao Y, Kodadek T. (2014) Split-and-pool synthesis and characterization of peptide tertiary amide library. J Vis Exp. (88):e51299. Doran TM, Kodadek T. (2014) A liquid array platform for the multiplexed analysis of synthetic molecule-protein interactions. ACS Chem Biol. 9(2):339-46. Kodadek T. (2013) A jack of all trades to combat drug-resistant Gram-negative bacteria. Chem Biol. 20(10):1202-3. Rzuczek SG, Gao Y, Tang ZZ, Thornton CA, Kodadek T, Disney MD. (2013) Features of modularly assembled compounds that impart bioactivity against an RNA target. ACS Chem Biol. 8(10):2312-21 Clark, L.F. and Kodadek, T. (2013) Advances in blood-based protein biomarkers for Alzheimer’s disease. Alzheimer’s Research & Therapy 5, 18-25. Sarkar, M., Pascal, B.D., Steckler, C., Micalizio, G.C., Kodadek, T. and Chalmers, M.J. (2013) Decoding split and pool combinatorial libraries with electron transfer dissociation tandem mass spectrometry. J. Amer. Soc. Mass Spec. 24, 1026-1036. Gao, Y. and Kodadek, T. (2013) Synthesis and Screening of Stereochemically Diverse Combinatorial Libraries of Conformationally Restrained Peptide Tertiary Amides. Chem. & Biol. 20, 360-369. Raveendra, B., Hao, W., Baccala, R., Reddy, M.M., Schilke, J., Bennett, J.L., Theofilopoulos, A.N. and Kodadek, T. (2013) Discovery of peptoid ligands for anti-Aquaporin 4 antibodies. Chem. & Biol. 20, 351-359 Suwal, S. and Kodadek, T. (2013) Synthesis of Libraries of Peptidomimetic Compounds Containing A 2-Oxopiperazine Unit In The Main Chain. Org. Biomol. Chem. 11, 2088 – 2092.