Cynthia M. Dupureur, Interim Department Chair
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Chemistry & Biochemistry: Summer 2015
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Professor Harris joined the UM-St. Louis faculty in the Fall of 1988. He received both his B.S. and his Ph.D. from Texas A&M University, and was a Postdoctoral Associate at the University of California-Berkeley. Prior to coming to St. Louis, he held faculty positions at the University of California at Davis and the University of Idaho.
The insolubility of Fe3+ at physiological pH requires that organisms transport this essential nutrient as a metal chelate. The transport agent in mammals is the serum protein transferrin. Several aspects of transferrin chemistry are being studied by Dr. Harris' group. One is the kinetics of iron release to low molecular weight chelating agents. The mechanism for this reaction is very complex. There appear to be two pathways for iron release, and the relative importance of each pathway varies among different types of ligands. The reaction rates are also strongly affected by the binding of inorganic anions to an allosteric regulatory site on the protein. This research is relevant to normal iron metabolism and to the search for an effective drug for treating iron toxicity.
In addition to its role in iron metabolism, transferrin also acts as the primary transport agent for a variety of toxic and therapeutic metal ions. Dr. Harris group has been heavily involved in evaluating the role of transferrin in the serum transport of Al3+ . Studies are being conducted on the binding of aluminum by serum chelating agents, on the exchange of aluminum between transferrin and low molecular weight ligands, and on computer models for the speciation of Al in serum and cerebral spinal fluid.
Many of the current studies on transferrin involve the use of recombinant transferrin and single point mutations of transferrin. These studies involve collaborations with molecular biologists, who produce specific mutants for chemical studies. These collaborative efforts now make it possible to evaluate the influence of specific amino acid side chains on metal binding affinities and the rates of metal exchange.
The Harris group has had a longstanding interest in the transferrin binding affinities of different metal ions. Now that there is a significant data base of binding affinities available, this research is focusing more on evaluating the specific molecular factors that govern metal binding affinity and selectivity. This includes the development of acid-base parameters for the protein and selected metal ions that will enable one to predict the transferrin binding constants for metals like Pu4+, which are extremely hazardous and thus difficult to study directly.
″Crystal structure of pyridoxal amino methyl phosphonic acid (PYRAMPA) and its stability constants with Al3+,″ Y. Z. Hamada, W. R. Harris and N. P. Rath, Int. J. Green Nanotech, 2013, 5, 1
"A speciation model of essential trace elements in phloem" W. R. Harris, D. R. Sammons and R. C. Grabiak, J. Inorg. Biochem. 2012, 116, 140.
"Computer Simulation of the Interactions of Glyphosate with Metal Ions in Phloem," W. R. Harris, R. D. Sammons, R. C. Grabiak, A. Mehrsheikh, and M. S. Bleeke, J. Ag. Food. Chem. 2012, 60, 6077.
"Anion binding properties of the transferrins. Implications for function," W. R. Harris, Biochim. Biophys. Acta, General Subjects, 2012, 1820, 348
"Chelating compounds and immobilized tethered chelators," R. A. Yokel, W. R. Harris, C. D. Spilling, R. J. Kuhn and S. Dawadi, U.S. Pat. Appl. Publ. 2012, US 2012-0061325 A120120315.
"Allosteric effects of sulphonate anions on the rates of iron release from Serum Transferrin", R. Sharma and W. R. Harris, J. Inorg. Biochem., 2011, 105, 1148
"New Chelating Ligands with Potential for Pharmaceutical Applications", Y. Z. Hamada and W. R. Harris, Synth. React. Inorg. Metal-Organic, and Nano-Metal Chem. 2010,40, 45.
"Chelating compounds, intermediates for chelators and resin-immobilized tethered chelators and removal of metal ions from aqueous solutions", R. A. Yokel, W. R. Harris, C. D. Spilling and C-G. Zhan, U.S. Pat. Appl. Publ. 2009, US 2008-104066
"The influence of citrate, maltolate and fluoride on the gastrointestinal absorption of aluminum at a drinking water-relevant concentration: A Al-26 and C-14 study", Y. Zhou, W. R. Harris and R. A. Yokel, Journal of Inorganic Biochemistry 2008, 102 798.
"Borate Binding to Siderophores: Structure and Stability", W. R. Harris, S. A. Amin, F. C. Kuepper, D. H. Green and C. J. Carrano, J. Am. Chem. Soc. 2007, 129, 12263.
"Boron Binding by a Siderophore Isolated from Marine Bacteria Associated with the Toxic Dinoflagellate Gymnodinium catenatum", S. A. Amin, F. C. Kuepper, D. H. Green, W. R. Harris and C. J. Carrano, J. Am. Chem. Soc., 2007, 129, 478.
"Determination of the binding constant of terbium-transferrin", S. Abdollahi and W. R. Harris, Iran J. Chem. Chem Eng., 2006, 25, 45.
"Stability constants and multinuclear NMR measurements of phosphonic acid derivatives with aluminum in aqueous solutions", Z. Y. Hamada and W. R. Harris, Inorg. Chim. Acta., 2006, 359, 1135.
"Modeling and Separation-Detection Methods to Evaluate the Speciation of Metals for Toxicity Assessment", J. Caruso, Joseph, R. Wuilloud, J. Altamirano and W. R. Harris,J. Toxicol. Environ. Health, 2006, B9, 41.
"Effect of Ligand Structure on the Pathways for Iron Release from Human Serum Transferrin", C. E. Brook, W. R. Harris, C. D. Spilling, P. Wang, J. Harburn and S. Srisung, Inorg. Chem., 2005, 44, 5183.