41] Syntheses and applications of flavin analogs as active site probes for flavoproteins

Abstract

This chapter discusses the synthesis of a range of new flavins and their potentials as active-site probes for flavoproteins. A few new flavins with substitutions such as trifluoromethyl, chloro, azido, carbonyl, and mercapto at the N-5 position are successfully synthesized. The selective introduction of fluorine into biologically interesting molecules is fast emerging as an effective tool because of the unique properties of this halogen. Because fluorine is smallest next to hydrogen, its substitution often results in minimal steric constraints. Also, because fluorine can act as hydrogen bond acceptor, the replacement of hydroxyl with fluorine allows the molecule to retain its properties. The N-10 ribityl side chain of flavins is generally considered as only a binding anchor in flavoproteins, with no positive role in catalysis. However, the X-ray crystal structures of various flavoproteins such as Old Yellow Enzyme, acyl-CoA dehydrogenase, glutathione reductase, and lipoamide dehydrogenase show involvement of ribitylhydroxylgroups in hydrogen bonds that can regulate catalytically important amino acid residues.