Modeling Flavin Coenzyme Function in Peptides and Proteins

Modeling Flavin Coenzyme Function in Peptides and Proteins 

The first and most extensively examined system was the hydrolytic enzyme papain. A variety of isomeric a-bromoacetylisoalloxazines were used to selectively tether a flavin moiety to the active site cysteine residue. Different isomeric linkages were proposed to allow orientations of the flavin relative to the substrate binding site which would favor reactions with a bound substrate [65]. 

These flavopapains (Fig. 19) were shown to be effective redox catalysts for the oxidation of hT-alkyl-l,4-dihydronicotinamides. The localization of the flavin moiety adjacent to the hydrophobic binding groove of the active site further allowed the constructs to exhibit substrate selectivity and, in some cases, saturation kinetics. The most effective flavopapain was the 8-isomer (FP-8) which reacted rapidly with a variety of M-alkyl-1,4-dihydronicotinamides. The best substrate was N-hexyl-l,4-dihydronicotinamide for which the of its 

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