Tailor Made LasR Agonists Modulate Quorum Sensing in Pseudomonas aeruginosa
| Autor: | Boaz Inbal, Michael M. Meijler, Pnina Krief, Antonia Delago, Nira Rabin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Molecular Dynamics Simulation 010402 general chemistry medicine.disease_cause 01 natural sciences Biochemistry Structure-Activity Relationship 03 medical and health sciences 4-Butyrolactone Bacterial Proteins Homoserine medicine Secretion Physical and Theoretical Chemistry Binding site 030304 developmental biology chemistry.chemical_classification 0303 health sciences Dose-Response Relationship Drug Molecular Structure Chemistry Pseudomonas aeruginosa Organic Chemistry Quorum Sensing Biological activity Ligand (biochemistry) 0104 chemical sciences 3. Good health Quorum sensing Trans-Activators lipids (amino acids peptides and proteins) Autoinducer Lactone |
| Zdroj: | Organic & Biomolecular Chemistry |
| ISSN: | 1477-0520 |
| DOI: | 10.1039/c3ob41377b |
| Popis: | The primary quorum sensing system in the opportunistic pathogen Pseudomonas aeruginosa is regulated through the synthesis and secretion of N-3-oxo-dodecanoyl-L-homoserine lactone (C12) which binds the transcriptional activator LasR. In this study we report the design, synthesis and biological evaluation of new analogs of C12. Analysis of the autoinducer binding site cavity of LasR revealed a positively charged cavity near the center of bound C12. Accordingly, we synthesized two piperidine-C12 diastereoisomers and tested their biological activity. Both analogs proved to be strong LasR agonists that showed a synergistic effect when presented together with the natural ligand. Moreover, binding of the analogs resulted in phenotypic changes characteristic of QS controlled receptor activation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|