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.
Alfaro
Joshua F
JF
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.
Zhang
Tiao
T
Wynn
DonRaphael P
DP
Karschner
Erin L
EL
Zhou
Zhaohui Sunny
ZS
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