This proposal discusses strategies for developing models for metalloenzymes possessing pterin cofactors. Enzymes relevant to the proposed research are phenylalanine hydroxylase and the molybdenum oxo-transferases such as xanthine oxidase, sulfite oxidase and aldehyde reductase. These enzymes have important roles in human metabolism where they are involved in amino acid synthesis, purine metabolism, and sulfite detoxification. Deficiencies in these enzymes cause common illnesses such as phenylketonuria(PKU), mental illness, and gout. Transition metals and pterins are located at the catalytically active sites in the above enzymes. The function of the metal and the pterin at these sites is not completely understood. In part, this incomplete understanding is due to the undeveloped area of metal-pterin chemistry. The proposed research will investigate reactions of transition metals with pterins. These studies will focus on the biologically relevant metals iron, copper and molybdenum and will incorporate tetrahydro- and dihydro-pterin reagents. The investigation will attempt to a) synthesize discrete, isolable metal-pterin complexes and b) study the redox reactions that occur between metal ions and reduced pterins. Formation of isolable completes will allow full characterization by spectroscopic, structural and electrochemical techniques. New methodologies that will be applied to this research problem are the use of non-aqueous solvents and the use of the sterically demanding tridentate tris(pyrazolyl)borate ligands. The study is designed to provide model compounds and model reactions that can be used to develop mechanisms for the above enzymes.
| Schluter, S F; Beischel, C J; Martin, S A et al. (1990) Sequence analysis of homogeneous peptides of shark immunoglobulin light chains by tandem mass spectrometry: correlation with gene sequence and homologies among variable and constant region peptides of sharks and mammals. Mol Immunol 27:17-23 |
