(Principal Investigator's) This proposal describes the design, synthesis and physical study of models for flavoenzyme catalysis. Specifically, we will explore the role of conformation, substituents and hydrogen bonding on the redox properties of flavins. We propose to synthesize flavins which have build-in conformational biases; by designing such models, we can isolate the role of conformation on the flavin redox chemistry. To fully understand the role of conformation on flavin redox properties, we must also determine the electronic influence of substitution on the benzene subnucleus of flavins. This will be accomplished by synthesizing flavins with various substituents at C6-C9 and examining their influence on reduction potential. It is proposed that hydrogen bonding of the flavin nucleus to the protein backbone can influence the geometry and redox properties of the co-factor. In addition to the conformationally biased flavins, we will also synthesize model which can provide specific hydrogen bonds to N1 and N5 of flavins. Flavin models that explore the influence of cooperative hydrogen bond networks will also be studied. All flavin models will be studied by cyclic voltammetry in aqueous buffer as well as non-aqueous media and by kinetic methods.
| Guo, Fengli; Chang, Bryan H; Rizzo, Carmelo J (2002) An N1-hydrogen bonding model for flavin coenzyme. Bioorg Med Chem Lett 12:151-4 |
| Rizzo, C J (2001) Further computational studies on the conformation of 1,5-dihydrolumiflavin. Antioxid Redox Signal 3:737-46 |
| Reibenspies, J H; Guo, F; Rizzo, C J (2000) X-ray crystal structures of conformationally biased flavin models. Org Lett 2:903-6 |
