475208-94-7Relevant academic research and scientific papers
Role of the CAI-1 fatty acid tail in the Vibrio cholerae quorum sensing response
Perez, Lark J.,Ng, Wai-Leung,Marano, Paul,Brook, Karolina,Bassler, Bonnie L.,Semmelhack, Martin F.
, p. 9669 - 9681 (2013/01/16)
Quorum sensing is a mechanism of chemical communication among bacteria that enables collective behaviors. In V. cholerae, the etiological agent of the disease cholera, quorum sensing controls group behaviors including virulence factor production and biofilm formation. The major V. cholerae quorum-sensing system consists of the extracellular signal molecule called CAI-1 and its cognate membrane bound receptor called CqsS. Here, the ligand binding activity of CqsS is probed with structural analogues of the natural signal. Enabled by our discovery of a structurally simplified analogue of CAI-1, we prepared and analyzed a focused library. The molecules were designed to probe the effects of conformational and structural changes along the length of the fatty acid tail of CAI-1. Our results, combined with pharmacophore modeling, suggest a molecular basis for signal molecule recognition and receptor fidelity with respect to the fatty acid tail portion of CAI-1. These efforts provide novel probes to enhance discovery of antivirulence agents for the treatment of V. cholerae.
Development of novel EDG3 antagonists using a 3D database search and their structure-activity relationships
Koide, Yuuki,Hasegawa, Takeshi,Takahashi, Atsuo,Endo, Akira,Mochizuki, Naoki,Nakagawa, Masako,Nishida, Atsushi
, p. 4629 - 4638 (2007/10/03)
Sphingosine-1-phosphate (S1P) is an intracellular second messenger and an extracellular mediator through endothelial differentiation gene (EDG) receptors, which are a novel class of G-protein-coupled receptors. Although EDG has attracted much attention because of its various roles, no selective agonists or antagonists have yet been developed. This could account for the delay in clarifying the physiological roles of members of the EDG family. Because precise structural information on EDG receptors is not yet available, pharmacophore models were generated based on structural information for S1P using the rational drug design software Catalyst. Novel antagonists, 2-alkylthiazolidine-4-carboxylic acids, were retrieved from a three-dimensional database search using the pharmacophore models, and these showed activity for EDG3. On the basis of their nonphosphoric acid structure, more potent antagonists, 2-(m- or p-heptylphenyl)thiazolidine-4-carboxylic acid, were developed.
