Leeper Group



F. J. Leeper and M. Rock
"Interaction of Analogues of Porphobilinogen with Porphobilinogen Deaminase"
J. Chem. Soc., Perkin Trans. 1,1996, 2643-2649. Full Text

2-Methylporphobilinogen and 8,9-dehydroporphobilinogen are only weak inhibitors of porphobilinogen deaminase (hydroxymethylbilane synthase). The phosphonate analogue and 9-fluoroporphobilinogen are good inhibitors, however, and also act as slow substrates (the first unnatural substrates known for this enzyme). The particularly strong inhibition shown by the fluoro analogue is shown to be due to the slow regeneration of free enzyme once the compound has become covalently bound to it. This results in a sigmoidal dependence of rate vs. [substrate].

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Department of Chemistry
University of Cambridge