Ph.D., chemistry (synthetic/medicinal chemistry), University of Montana, Missoula, Mont.
Bachelor of Science, chemistry, Central Washington University, Ellensburg, Wash.
Fellowships & Additional Training
Post Doctoral Research: Shafizadeh Rocky Mountain Center for Wood and Carbohydrate Chemistry: The University of Montana, Missoula, Mont. 2005-2007
Post Doctoral Research: Human BioMolecular Research Institute, San Diego, Calif. 2002-2005
Chemical biology portion of the Integrated Pharmaology series.
Synthetic Medicinal Chemistry, Neuroscience, Drug Metabolism and Disposition, and Pharmacokinetics.
Specifically, our group is preparing libraries of small molecules to target the cys-loop receptor family (nicotinic acetylcholine and 5-HT3 receptors, specifically). These compound libraries are assayed using a high throughput screening method based upon the acetylcholine binding proteins. Lead compounds are then co-crystallized with the binding proteins to obtain X-ray crystal structures of the resulting complex. This work is done in collaboration with Todd T. Talley at Idaho State University College of Pharmacy. Our groups are using these tools to develop selective ligands for the potential treatment of nicotine addiction and neurodegenerative diseases.
Our group also has a component directed towards carbohydrate and polymer chemistry for the development of novel antibacterial agents, cell Targeted, non-Viral drug and gene delivery agents and biodegradable gels, plastics and glues.
- Novel antibacterial agents: Polymeric quaternary ammonium compounds have a unique set of properties for the selective destruction of bacteria with the unique mode of action that avoids the possibility of the bacteria becoming resistant to the antibiotic. The chemistry used in the design and preparation of the polymeric antibiotics affords a large opportunity for chemical functionalization and optimization. The polymers can be biodegradable, non-biodegradable, water soluble, impervious to water and selective for certain strains of bacteria over others, as well as many more features.
- Cell Targeted, Non-Viral Drug and Gene Delivery Agents: We have developed a series of polycationic macromolecules with the ability to condense plasmid DNA with the ability of transfecting mammalian cells. The materials are unique in that once they are taken into the cell and release their cargo they are slated for destruction within the cell and, specifically designed, to release a monomeric unit that has been demonstrated to have chemotherapeutic value against some carcinogens. The chemical structure of the polymers also affords the chemist a number of “handles” to append the backbone to selectively target the polymer-payload polyplexes to specific cells via cell surface receptors.
- Biodegradable Gels, Plastics and Glues: Although this may not sound oriented towards pharmaceutical sciences, it most certainly is. The monomeric units for the materials in question are directly prepared from corn sugar, connected together with peptide bonds and have been shown to release bioavailable nutrients upon their breakdown. These materials are being developed for use in biomedical applications such as adhesives for wound dressings, tissue engineering and other regenerative medicine.
We also develop Phosphonate analogues of -Ketoacids as Mechanistic Probes of -Ketoacid Dehydrogenase Complexes and Aminotransferases. This project focuses on the preparation of phosphonate analogues of the a-ketoacids. Our group has experience in the preparation and utilization of phosphonates in a number of applications ranging from the inhibition of the -ketoglutarate dehydrogenase complex, the branched chain dehydrogenase complex and branched chain amino acid transaminases. Our group focuses on the preparation of the small molecules and collaborates with a number of groups in the screening to the novel small molecules including Arthur J. L. Cooper (New York Medical College), Gary Gibson (Weill Medical College of Cornell University), Kenneth Hensley (University of Toledo), Hui Feng (Boston University School of Medicine).
Development of stable isotope analogues of medicinally relevant compounds for use in analytical chemistry. Using our experience in synthetic organic chemistry, we have made and are in the process of making more stable isotope isoforms of small molecules of therapeutic interest. Besides having our own research programs, we are always open and available to help out in the preparation of any small molecule or macromolecule, which may prove beneficial to our companions in science.
Tsikas D, Denton TT, Cooper AJ. Comment on Absorption of Aminoethyl Cysteine Ketimine Decarboxylated Dimer in Mice: Effect on Plasma Antioxidant Potential. J. Agric. Food Chem. 2013, 61 (25), 6122–6124.
Baker MJ, Denton TT, Herr C. An explanation for why it is difficult to form slush nitrogen from liquid nitrogen used previously for this purpose. Cryobiology 2012, 66 (1), 43-46.
Tsikas D, Evans CE, Denton TT, Mitschke A, Gutzki FM, Pinto JT, Khomenko T, Szabo S, Cooper AJ. Stable isotope gas chromatography-tandem mass spectrometry determination of aminoethylcysteine ketimine decarboxylated dimer in biological samples. Anal. Biochem. 2012, 430(1), 4-15.
Gibson GE, Chen HL, Xu H, Qiu L, Xu Z, Denton TT, Shi Q. Deficits in the mitochondrial enzyme α-ketoglutarate dehydrogenase lead to Alzheimer's disease-like calcium dysregulation. Neurobiol Aging. 2012, 33(6), 1121.e13-24.
Denton TT, Hardcastle KI, Dowd MK, Kiely DE. Characterization of D-glucaric acid using NMR, X-ray crystal structure, and MM3 molecular modeling analyses. Carbohydr Res. 2011, 346(16), 2551-2557.
Shimizu M, Denton TT, Kozono M, Cashman JR, Leeder JS, Yamazaki H. Developmental variations in metabolic capacity of flavin-containing mono-oxygenase 3 in childhood. Br. J. Clin. Pharmacol. 2011, 71(4), 585-91.
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