|
Nick received his B.S. in 1976 and his Ph.D. in 1979 in Chemistry from Drexel University in Philadelphia. He then moved to Fort Collins, CO and took a postdoctoral position at Colorado State University from 1979-81 in the lab of Albert I. Meyers. He joined the faculty at the University of Idaho in 1981, where he rose through the ranks to professor of Chemistry, and in 2004 was named the Distinguished Science Communicator by the Idaho Academy of Science. Nick was named Professor of Medicinal Chemistry at the University of Montana and joined CSFN in 2007.
_______________________________________________________________
INTERESTS OF THE NATALE LABORATORY
Professor Natale's research is focused on how biological activity relates to structure, especially as regards conformation and chirality. Three classes of compounds under study in his research group have produced interesting recent discoveries. In the area of neurotransmitters, related to ligands of the endogenous AMPA Receptor (Amino-Methylisoxazole-Propionic Acid), structure based design has lead to a new series of analogs which hold promise for treatment of disorders such as stroke and Alzheimer's disease.
Molecules that bind in two different modes to DNA may be connected with a link that pre-organizes the two parts to hold the correct shape in three dimensions. These intercalating lexitropsins show promising anticancer activity in preliminary screens performed by the National Cancer Institute, and their activity may result from the inhibition of transcription. The goal is to increase efficacy and selectivity by attempting to recognize a specific DNA sequence unique to the disease process.
Antihypertensive 4-Isoxazole-1,4-dihydropyridines show a pronounced enantioselectivity of biological action, with the (+)- eutomer exhibiting near nanomolar binding to the target membrane bound ion channel. This leads to a hypothesis for the structure of the ion channel binding site, and a lipophilic series of analogs consistent with that hypothesis.
Projects underway include the application of isoxazole chemistry developed in his labs toward drug discovery directed at Type 2 Diabetes (T2D) and resistant and emerging infectious diseases.
_______________________________________________________________
SELECTED PUBLICATIONS (2000 to present)
Jared K. Nelson, Christopher T. Burns, Miles P. Smith, Brendan Twamley and N.R. Natale, "Synthetic Utility of Epoxides for Chiral Functionalization of Isoxazoles", Tetrahedron Lett., 2008, 49, 3078-82. Chun Li, Brendan Twamley and N.R. Natale, “Preparation and Crystal Structures of Two 3-Anthracenyl Isoxazolyl Sulfonamides”, J. Heterocycl. Chem., 2008, 45, 259-264.
Brendan Twamley, Monika Szabon-Watola, Shikha Sharmaand Nicholas R. Natale, Ethyl-5-methyl-4-(2-bromomethyl-5,5-dimethyl-1,3-dioxan-2-yl)isoxazole-3- carboxylate “, Acta Cryst., 2007, E63, o2258-o2260.
“Can Selective Ligands for Glutamate Binding Proteins be Rationally Designed?“, N.R. Natale, K. Magnusson, and J.K. Nelson, Current Topics in Medicinal Chemistry , Symposium–in-print, 2006 , 6, 823-846.
David J. Burkhart and N.R. Natale,“Isoxazole Ionotropic Glutamate Neurotransmitters”, Current Medicinal Chemistry, invited review, 2005, 12, 617-627.
David J. Burkhart, Andrew R. McKenzie, Jared K. Nelson, Katherine I. Myers, Xue Zhao, Kathy R. Magnusson, and Nicholas R. Natale, “The Catalytic Asymmetric Synthesis of Glutamate Analogues”, Org. Lett., 2004, 6, 1285-8.
Gerald Zamponi, Stephanie C. Stotz, Richard J. Staples, Tina M. Andro, Jared K. Nelson, Victoria Hulubei, Alex Blumenfeld, and N.R. Natale , "Unique Structure Activity Relationship of 4-Isoxazolyl-1,4-dihydropyridines" J. Med. Chem., 2003, 46, 87-96.
N. R. Natale, "Building Bridges to Native American Students: Chapter Outreach Activities at the University of Idaho", invited contribution, in Chemistry (American Chemical Society), 2002, 12, November/December , 15-17.
Xiaochun Han, Chun Li, Kevin C. Rider, Alex Blumenfeld, Brendan Twamley, and N.R. Natale "The Isoxazole as a linchpin for molecules which target folded DNA conformations: Selective Lateral Lithiation and Palladation", Tetrahedron Lett. , 2002, 43, 7673-7377.
David J. Burkhart, Brendan Twambley and N.R. Natale, "A New Direct Synthesis of ACPA and analogs", Tetrahedron. Lett., 2001, 42, 8415-8418.
N.R. Natale, "Learning from the Hantzsch Synthesis", Chemical Innovation (American Chemical Society), 2000, 30(11), 22-28.
|
