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Our research is centered on medicinal and biophysical chemistry, with emphasis in the areas of nuclear magnetic resonance (NMR) spectroscopy in biological systems, and developing antimalarial drugs. I also direct the Portland State University NMR facility, which actually serves the entire Portland area.We apply a variety of tools, depending on the nature of a particular problem. These tools include organic synthesis, electronic spectroscopy, NMR spectroscopy, and computer modeling. The following are specific projects currently being investigated.
Reversed Chloroquines as Antimalarial Agents:
Chloroquine (CQ) is one of the safest and most effective drugs ever developed, but resistance has emerged against it. We have developed a way to modify CQ to circumvent this problem. Work is ongoing to develop these drugs into a practical and inexpensive treatment for malaria, a disease that is actually a growing worldwide problem.
Protein Structure/Function Studies:
Collagens. After so many years as a textbook case, we still don’t really know the canonical reasons for the stability of collagen, our most abundant protein. We are particularly interested in glycosylated collagens, lacking hydroxyproline.
Subtilisin & Furin. These proteins are produced in vivo as precursors, including an intramolecular chaperone domain. Questions about dynamics and structure are being addressed by NMR. These systems are important because the propeptide motifs are conserved within this type of protein, and may be important for protein folding in general.
Tobacco Smoke Chemistry.
Once-secret ‘internal’ tobacco industry documents discuss how adding bases to cigarette tobacco can increase the proportion of free-base nicotine in the smoke particulate matter (PM), and therefore enhance the smoke “impact”. We are able to use NMR spectroscopy to probe tobacco smoke particulate matter to find the fraction of free-base nicotine in a direct way. |
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Optimization of Xanthones for Antimalarial Activity, the 3,6-w-diethylaminoalkoxyxanthone Series. J.X. Kelly, R. Winter, D.H. Peyton, D.J. Hinrichs, & M.K. Riscoe (2002), Antimicrob. Agts. Chemo., 46, 144-150.
Antileishmanial Drug Development: Exploitation of Parasite Heme Dependency.
J.X. Kelly, M.V. Ignatuschchenko, R.W. Winter, H.G.
Bouwer, D.H. Peyton, D.J. Hinrichs, & M. Riscoe
(2002), Mol. Biochem. Parasitol., 123, 47-54.
A Spectroscopic Investigation of the Binding Interactions Between 4,5-Dihydroxanthone and Heme. J.X. Kelly, R. Winter, M. Riscoe, & D.H. Peyton (2001), J. Inorg.
Biochem., 86, 617-625.
Sweet is Stable: Glycosylation stabilizes collagen. J.G. Bann, D.H. Peyton, & H.P. Bächinger (2000), FEBS
Lett., 473, 237-240.
Modulation of Dimerization, Binding, Stability, and Folding by Mutation of the Neurophysin Subunit Interface. S. Eubanks, T.L. Nguyen, D.H. Peyton, & E. Breslow (2000), Biochemistry,
39, 8085-8094.
Expression, Folding, and Thermodynamic Properties of the Bovine Oxytocin-Neurophysin Precursor: Relationships to the Intermolecular Oxytocin-Neurophysin Complex. S. Eubanks, M. Lu, D.H. Peyton, & E. Breslow (1999), Biochemistry, 38,
13530-13541.
Proton Resonance Assignments and Ligand Exchange Kinetics in High-Spin and Mixed-Spin Complexes using Two Dimensional Exchange Spectroscopy. Y. Luo, D.H. Peyton, & S. Yee (1998), Biochim. Biophys. Acta, 1388, 66-76.
Solution Structures of Human Immunodeficiency Virus Type I (HIV-1) and Moloney Murine Leukemia Virus (MoMLV) Capsid Protein Major Homology Region Peptide Analogs by Nuclear Magnetic Resonance Spectroscopy. C.B. Clish, D.H. Peyton, & E. Barklis (1998), Eur. J. Biochem.,
257, 69-77.
Spectroscopic Study of an HIV-1 Capsid Protein Major Homology Region Peptide Analog. C.B. Clish, D.H. Peyton,
& E. Barklis (1996), FEBS Lett., 378, 43-47.
Binding of Phosphocholine-Carrier Conjugates to the Combining Site of Antibodies Maintains a Conformation of the Hapten. E. Barbar, T. Martin, M.B. Rittenberg, & D.H. Peyton (1996), Biochemistry, 35, 2958-2967.
Variable-temperature Study of the Heme-reorientation Process in Equine Myoglobin. S. Yee & D.H. Peyton (1995), Biochim. Biophys. Acta 1252, 295-299.
NMR behavior of the aromatic protons of bovine neurophysin-I and its peptide complexes: implications for solution structure and for function. E. Breslow, V.Sardana, R. Deeb, E. Barbar, & D. H. Peyton (1995), Biochemistry, 34, 2137-2147.
Roles of heme iron-coordinating histidine residues of human hemopexin expressed in baculovirus-infected insect cells. T. Satoh, H. Satoh, S. Iwahara, Z. Hrkal, D.H. Peyton, & U. Muller-Eberhard (1994), Proc. Natl. Acad. Sci. USA, 91, 8423-8427.
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