1. Bioorg Med Chem. 2009 Sep 15;17(18):6699-706. Epub 2009 Jul 26.

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

Wnuk SF, Robert J, Sobczak AJ, Meyers BP, Malladi VL, Zhu J, Gopishetty B, Pei D.

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

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.

PMCID: PMC2765115 [Available on 2010/9/15]
PMID: 19682914 [PubMed - indexed for MEDLINE]