In collaboration with the Gervay-Hague and Kurth groups at UC Davis, we are applying several computational methods to facilitate the design of enzyme inhibitors and other potential drug compounds.
One technique we employ is automated docking of potential inhibitor structures into enzyme active sites. We are experimenting with different docking algorithms as well as different approaches for applying these methods to high-throughput screening of libraries of potential inhibitors.
We are also using "principal moment of inertia" analyses to characterize and quantify the diversity of compound libraries.
In addition, we are using quantum chemical methods to rationalize and predict stereoselectivities for reactions used to synthesize potentially active compounds, as well as conformational preferences of potential drugs.
Yoo, C. L.; Olmstead, M. M.; Tantillo, D. J.; Kurth, M. J. Tetrahedron Lett. 2006, 47, 477-481: "Synthesis of 2H-Pyrroles via the 1,3-Dipolar Cycloaddition of Nitrile Ylides with Acrylamides"
Meadows, D. C.; Tantillo, D. J.; Gervay-Hague, J. ChemMedChem 2006, 1, 959-964: "Correlation of Biological Activity with Active Site Binding Modes of Geminal Disulfone HIV-1 Integrase Inhibitors"
Carpenter, R. D.; DeBerdt, P. B.; Holden, J. B.; Milinkevich, K. A.; Min, T.; Willenbring, D.; Fettinger, J. C.; Tantillo, D. J.; Kurth, M. J. J. Comb. Chem. 2008, 10, 225-229: "Design and Synthesis of Propeller-shaped Dispiroisoxazolopiperidinochromanones"
Yu, G. J.; Yoo, C. L.; Yang, B.; Lodewyk, M. W.; Meng, L.; El-Idreesy, T. T.; Fettinger, J. C.; Tantillo, D. J.; Verkman, A. S.; Kurth, M. J. J. Med. Chem. 2008, 51, 6044-6054: "Potent s-cis-Locked Bithiazole Correctors of (delta)F508-Cystic Fibrosis Transmembrane Conductance Regulator Cellular Processing for Cystic Fibrosis Therapy"
Meng, L.; Wang, S. C.; Fettinger, J. C.; Kurth, M. J.; Tantillo, D. J. Eur. J. Org. Chem. 2009, 1578-1584: "Controlling Selectivity for Cycloadditions of Nitrones and Alkenes Tethered by Benzimidazoles: Combining Experiment and Theory"
Lodewyk, M. W.; Kurth, M. J.; Tantillo, D. J. J. Org. Chem. 2009, 74, 4804-4811: "Mechanisms for Formation of Diazocinones, Pyridazines, and Pyrazolines from Tetrazines - Oxyanion-Accelerated Pericyclic Cascades?"
Ye, L.; Haddadin, M. J.; Lodewyk, M. W.; Ferrieri, A.; Fettinger, J. C.; Tantillo, D. J.; Kurth, M. J., submitted: "Cyclopenta[b]pyrroles from Triazines - Synthetic and Mechanistic Studies"
Jacquelyn Gervay-Hague, Dean J. Tantillo and D. Christopher Meadows: "Computational Studies and Biological Evaluation of Geminal Disulfones as HIV-1 Integrase Inhibitors." Lecture presented by Jacquelyn Gervay-Hague at the 230th ACS National Meeting, Washington, DC, August 28-September 1, 2005.
Liping Meng, Selina C. Wang, James C. Fettinger, Mark J. Kurth, and Dean J. Tantillo: "Experiment and Theory Study on the Cycloadditions of Nitrones and Alkenes Tethered by Benzimidazoles." Poster presented by Liping Meng at the 237th ACS National Meeting, Salt Lake City, UT, March 22-26, 2009; paper ORGN 150.
Philip P. Painter and Dean J. Tantillo: "Eclipsing Transition States and Their Role in Chiral Imidazoline Racemization." Poster presented by Phil Painter at the SYLICCO.09 Symposium, Davis, CA, July 23, 2009.
Henry B. Wedler, Christian S. Hamann, and Dean J. Tantillo: "TheTheoretical Hydration Energues of Biologically Relevant alpha-Ketoamides." Poster presented by Hoby Wedler at the SYLICCO.09 Symposium, Davis, CA, July 23, 2009.
Handeep Kaur and Dean J. Tantillo: "The Bacteria's Gift: A Mechanistic Study of the Synthesis of Pseudomonine." Poster presented by Handeep Kaur at the SYLICCO.09 Symposium, Davis, CA, July 23, 2009.
Christian S. Hamann, Nichole A. Reed, and Dean J. Tantillo: "Modeling the Conformational Isomerization of an Atropisomeric Farnesyl Transferase Inhibitor." Poster presented by Chris Hamann at the SYLICCO.09 Symposium, Davis, CA, July 23, 2009.
