Chemical synthesis of S-ribosyl-L-homocysteine and activity assay as a LuxS substrate

Gang Zhao; Wei Wan; Shahrzad Mansouri; Joshua F. Alfaro; Bonnie L. Bassler; Kenneth A. Cornell; Zhaohui Sunny Zhou

doi:10.1016/j.bmcl.2003.09.015

Chemical synthesis of S-ribosyl-L-homocysteine and activity assay as a LuxS substrate

Gang Zhao, Wei Wan, Shahrzad Mansouri, Joshua F. Alfaro, Bonnie L. Bassler, Kenneth A. Cornell, Zhaohui Sunny Zhou

Princeton University

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

Abstract

Bacterial quorum sensing is mediated by autoinducers, small signaling molecules generated by bacteria. It has been proposed that the LuxS enzyme converts S-ribosyl-L-homocysteine to 4,5-dihydroxy-2,3-pentanedione, the precursor of autoinducer 2 (AI-2). We report here a chemical synthesis of S-ribosyl-L-homocysteine and its analogue using Mitsunobu coupling. Chemically synthesized ribosylhomocysteine has been confirmed as a substrate for LuxS in both an enzyme assay and a whole cell quorum sensing assay. The chemical entities of products from the LuxS reaction were also established. Several ribosylhomocysteine analogues have been tested as LuxS inhibitors.

Original language	American English
Pages (from-to)	3897-3900
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	13
Issue number	22
DOIs	https://doi.org/10.1016/j.bmcl.2003.09.015
State	Published - Nov 17 2003

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2003.09.015

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title = "Chemical synthesis of S-ribosyl-L-homocysteine and activity assay as a LuxS substrate",

abstract = "Bacterial quorum sensing is mediated by autoinducers, small signaling molecules generated by bacteria. It has been proposed that the LuxS enzyme converts S-ribosyl-L-homocysteine to 4,5-dihydroxy-2,3-pentanedione, the precursor of autoinducer 2 (AI-2). We report here a chemical synthesis of S-ribosyl-L-homocysteine and its analogue using Mitsunobu coupling. Chemically synthesized ribosylhomocysteine has been confirmed as a substrate for LuxS in both an enzyme assay and a whole cell quorum sensing assay. The chemical entities of products from the LuxS reaction were also established. Several ribosylhomocysteine analogues have been tested as LuxS inhibitors.",

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T1 - Chemical synthesis of S-ribosyl-L-homocysteine and activity assay as a LuxS substrate

AU - Zhao, Gang

AU - Wan, Wei

AU - Mansouri, Shahrzad

AU - Alfaro, Joshua F.

AU - Bassler, Bonnie L.

AU - Cornell, Kenneth A.

AU - Zhou, Zhaohui Sunny

PY - 2003/11/17

Y1 - 2003/11/17

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AB - Bacterial quorum sensing is mediated by autoinducers, small signaling molecules generated by bacteria. It has been proposed that the LuxS enzyme converts S-ribosyl-L-homocysteine to 4,5-dihydroxy-2,3-pentanedione, the precursor of autoinducer 2 (AI-2). We report here a chemical synthesis of S-ribosyl-L-homocysteine and its analogue using Mitsunobu coupling. Chemically synthesized ribosylhomocysteine has been confirmed as a substrate for LuxS in both an enzyme assay and a whole cell quorum sensing assay. The chemical entities of products from the LuxS reaction were also established. Several ribosylhomocysteine analogues have been tested as LuxS inhibitors.

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Chemical synthesis of S-ribosyl-L-homocysteine and activity assay as a LuxS substrate

Abstract

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