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Bioorg Med Chem. 2009 Sep 15;17(18):6699-706. doi: 10.1016/j.bmc.2009.07.057. Epub 2009 Jul 26.

Inhibition of S-ribosylhomocysteinase (LuxS) by substrate analogues modified at the ribosyl C-3 position.

Author information

1
Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USA. wnuk@fiu.edu

Abstract

S-ribosylhomocysteinase (LuxS) catalyzes the cleavage of the thioether bond of S-ribosylhomocysteine (SRH) to produce homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD), which is the precursor of type 2 autoinducer for bacterial cell-cell communication. In this work, we have synthesized several SRH analogues modified at the ribose C3 position as potential inhibitors of LuxS. While removal or methylation of the C3-OH resulted in simple competitive inhibitors of moderate potency, inversion of the C3 stereochemistry or substitution of fluorine for C3-OH resulted in slow-binding inhibitors of improved potency. The most potent inhibitor showed a K(I)(*) value of 0.43 microM.

PMID:
19682914
PMCID:
PMC2765115
DOI:
10.1016/j.bmc.2009.07.057
[Indexed for MEDLINE]
Free PMC Article

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