The molybdenum cofactor consists, inter alia, of a pterin component termed molybdopterin complexed with molybdenum. It appears to be a universal cofactor for a wide variety of molybdenum-containing enzymes, acting as a link to bind the enzyme subunits to form an active enzyme, and functioning as an electron carrier. Serious physiological and neurological problems, and eventual death, are the consequences of a deficiency of this critical cofactor. Since urothione (a complex sulfur-containing tricyclic pteridine derivative normally found in urine) cannot be detected in the urine of molybdenum cofactor-deficient patients, it appears that urothione is a metabolic excretion product of the cofactor. It is the aim of this proposal to determine, or confirm, the structure of the pterin component (molybdopterin) of the molybdenum cofactor by total synthesis, and to synthesize by unequivocal procedures several (inactive and oxidized) forms of the cofactor, Form A and Form B, as well as urothione itself, in order to confirm their structures. Attempts will be made to prepare the active cofactor from synthetic molybdopterin, using both biochemical and chemical methods, and to form stable complexes of native molybdopterin which can be compared with synthetic complexes of known structure. Final structural identification of and synthetic access to the active cofactor are the eventual goals of this proposed research.
