The objectives of this research are to characterize the prosthetic group of the """"""""hemoprotein"""""""" myeloperoxidase, to then synthesize this heme and compare its properties to the native system in order to understand the mechanism of action of myeloperoxidase. The synthesis of vitamin B12 biosynthetic precursors Factors I, II and III is planned along with siroheme. The study of these and model isobacteriochlorins will be made in order to explain the mechanisms of action of the sulfite and nitrite reductases. Models for vitamin B12 will be synthesised and their chemistry, particularly that of the cobalt-carbon bond, will be studied in order to mimic and explain the mechanism of action of the vitamin B12 coenzyme. In addition, methods for the synthesis of pyrrolic, polypyrroles and pyrrolic macrocycles will be developed. Finally the organometallic chemistry of iron and model ruthenium porphyrins will be studied since such chemistry is involved in the misfunctioning of several hemeproteins such as hemoglobin, myoglobin and cytochrome P-450.
| Dolphin, D (1985) Cytochrome P450: substrate and prosthetic-group free radicals generated during the enzymatic cycle. Philos Trans R Soc Lond B Biol Sci 311:579-91 |
