Synthesis and biological activity of a potent optically pure autoinducer-2 quorum sensing agonist.

Autor: Ascenso OS; Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Apartado 127, 2780-901 Oeiras, Portugal., Torcato IM; Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Apartado 127, 2780-901 Oeiras, Portugal; Instituto Gulbenkian de Ciência, 2781-901 Oeiras, Portugal., Miguel AS; Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Apartado 127, 2780-901 Oeiras, Portugal., Marques JC; Rowland Institute at Harvard, 100 Edwin H. Land Boulevard, Cambridge, MA 02142, USA(2)., Xavier KB; Instituto Gulbenkian de Ciência, 2781-901 Oeiras, Portugal., Ventura MR; Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Apartado 127, 2780-901 Oeiras, Portugal. Electronic address: rventura@itqb.unl.pt., Maycock CD; Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Apartado 127, 2780-901 Oeiras, Portugal; Faculdade de Ciências da Universidade de Lisboa, Departamento de Química e Bioquímica, 1749-016 Lisboa, Portugal. Electronic address: maycock@itqb.unl.pt.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2019 Apr; Vol. 85, pp. 75-81. Date of Electronic Publication: 2018 Dec 20.
DOI: 10.1016/j.bioorg.2018.12.022
Abstrakt: Quorum sensing (QS) regulates population-dependent bacterial behaviours, such as toxin production, biofilm formation and virulence. Autoinducer-2 (AI-2) is to date the only signalling molecule known to foster inter-species bacterial communication across distantly related bacterial species. In this work, the synthesis of pure enantiomers of C4-propoxy-HPD and C4-ethoxy-HPD, known AI-2 analogues, has been developed. The optimised synthesis is efficient, reproducible and short. The (4S) enantiomer of C4-propoxy-HPD was the most active compound being approximately twice as efficient as (4S)-DPD and ten-times more potent than the (4R) enantiomer. Additionally, the specificity of this analogue to bacteria with LuxP receptors makes it a good candidate for clinical applications, because it is not susceptible to scavenging by LsrB-containing bacteria that degrade the natural AI-2. All in all, this study provides a new brief and effective synthesis of isomerically pure analogues for QS modulation that include the most active AI-2 agonist described so far.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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