PMID:11735509
| Citation |
Cushman, M, Yang, D, Kis, K and Bacher, A (2001) Design, synthesis, and evaluation of 9-D-ribityl-1,3,7-trihydro-2,6,8-purinetrione, a potent inhibitor of riboflavin synthase and lumazine synthase. J. Org. Chem. 66:8320-7 |
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| Abstract |
Reduction of 5-nitro-6-D-ribitylaminouracil (9) afforded 5-amino-6-D-ribitylaminouracil (1), which reacted with ethyl chloroformate to yield 5-ethylcarbamoyl-6-D-ribitylaminouracil (12). The latter compound was cyclized to 9-D-ribityl-1,3,7-trihydropurine-2,6,8-trione (13), which was found to be a relatively potent inhibitor of both Escherichia coli riboflavin synthase (K(i) 0.61 microM) and Bacillus subtilis lumazine synthase (K(i) 46 microM). Molecular modeling of the lumazine synthase-inhibitor complex indicated the possibility for hydrogen bonding between the Lys135 epsilon-amino group of the enzyme and both the 8-keto group and the 4'-hydroxyl group of the ligand. A bisubstrate analogue of the riboflavin synthase-catalyzed reaction, 1,4-bis[1-(9-D-ribityl-1,3,7-trihydropurine-2,6,8-trionyl)]butane (18), was also synthesized using a similar route and was found to be inactive as an inhibitor of both riboflavin synthase and lumazine synthase. |
| Links | |
| Keywords |
Bacillus subtilis/chemistry; Crystallography, X-Ray; Enzyme Inhibitors/chemical synthesis; Escherichia coli/chemistry; Hydrogen Bonding; Kinetics; Models, Molecular; Multienzyme Complexes/antagonists & inhibitors; Purines/chemical synthesis; Recombinant Proteins/chemistry; Ribitol/analogs & derivatives; Ribitol/chemical synthesis; Riboflavin Synthase/antagonists & inhibitors |
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