Synthesis of LuxS inhibitors targeting bacterial cell-cell communication.
[reaction: see text] Quorum sensing is a process by which bacteria sense cell density. This cell-cell communication process is mediated by autoinducers. A cross-species messenger, autoinducer-2 (AI-2) is produced from S-ribosyl-L-homocysteine by the LuxS enzyme. A proposed mechanism for LuxS is an aldose-ketose isomerization of S-ribosylhomocysteine followed by a beta-elimination. We report here the synthesis of two substrate analogues, S-anhydroribosyl-L-homocysteine and S-homoribosyl-L-cysteine, which prevent the initial and final step of the mechanism, respectively.
Department of Chemistry, School of Molecular Biosciences, Center for Integrated Biotechnology, Graduate Program in Pharmacology and Toxicology, Washington State University, Pullman, Washington 99164-4630, USA.
Joshua F
JF
Alfaro
Tiao
T
Zhang
DonRaphael P
DP
Wynn
Erin L
EL
Karschner
Zhaohui Sunny
ZS
Zhou
D001419:Bacteria / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D013437:Carbon-Sulfur Lyases; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013379:Substrate Specificity
D001426:Bacterial Proteins; C487472:S-ribosyl-L-homocysteine; D006710:Homocysteine; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria