Inhibition of mandelate racemase by alpha-fluorobenzylphosphonates.

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St Maurice M, Bearne SL, Lu W, Taylor SD

Inhibition of mandelate racemase by alpha-fluorobenzylphosphonates.

Bioorg Med Chem Lett. 2003 Jun 16;13(12):2041-4.

PubMed ID

12781191 [ View in PubMed

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Abstract

Mandelate racemase catalyzes the interconversion of the enantiomers of mandelic acid. The enzyme binds the intermediate analogues (R)- and (S)-alpha-fluorobenzylphosphonate, and alpha,alpha-difluorobenzylphosphonate with 100-2500 times less affinity than it exhibits for (R,S)-alpha-hydroxybenzylphosphonate at pH 7.5. This apparent low affinity, relative to that of alpha-hydroxybenzylphosphonate, arises from the altered pKa values of the alpha-fluorobenzylphosphonates. For example, (S)-alpha-fluorobenzylphosphonate is bound with the same affinity as the substrate at pH 7.5, but this affinity is increased approximately 6-fold at pH 6.3.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
(S)-Mandelic acid	Mandelate racemase	Ki (nM)	570000	N/A	N/A	Details
(S)-Mandelic acid	Mandelate racemase	Ki (nM)	590000	N/A	N/A	Details