Synthesis and biological activity of a potent optically pure autoinducer-2 quorum sensing agonist.
AI-2
DPD
DPD agonists
DPD analogues
Quorum sensing
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
22
06
2018
revised:
17
11
2018
accepted:
16
12
2018
pubmed:
3
1
2019
medline:
12
2
2020
entrez:
3
1
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30602129
pii: S0045-2068(18)30616-3
doi: 10.1016/j.bioorg.2018.12.022
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Bacterial Proteins
0
Carrier Proteins
0
Escherichia coli Proteins
0
LsrB protein, E coli
0
LuxP protein, Vibrio
0
Pentanones
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
75-81Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.