[Seminar] Synthesis of analogs, chemical probes and prodrugs based on the structure of AI-2
| When |
07 Jun, 2019
from
02:00 pm to 04:00 pm |
|---|---|
| Where | Auditorium |
| Add event to your calendar |
iCal
|
Title: "Synthesis of analogs, chemical probes and prodrugs based on the structure of AI-2"
Speaker: Vanessa Miranda
Affiliation: ITQB NOVA
Abstract: Quorum sensing (QS) regulates bacteria behaviours in response to the concentration of autoinducers in the environment. Autoinducer-2 (AI-2) is unique as it is produced and detected by many phylogenetically distinct bacteria. Currently, two receptors are known for AI-2, LuxP and LsrB. However, new classes of AI-2 receptors are hypothesised to exist as phenotypes regulated by AI-2 have been identified in species where LuxP and LsrB are absent. Previous work has been developed in our group on the synthesis of (S)-4,5-dihydroxypentane-2,3-dione (DPD) (AI-2 precursor) and analogues starting from methyl glycolate in optically pure form.
The discovery of new analogues which could function as agonists or antagonists of AI-2 activity is crucial for the modulation of the QS behaviours. The synthesis and the biological activity of a panel of C1 and C5 analogues will be presented.
In order to identify new AI-2 receptors we developed an efficient and reproducible synthesis of a novel chemical probe D-desthiobiotin-AI-2 which is binds both LuxP and LsrB class of receptors from different species of bacteria.
[
The gut microbiota is another important niche where the QS processes are crucial for the health of the organism. Previous results from Karina Xavier’ lab have shown that AI-2 influence the balance of the major phyla in the gut, Firmicutes, after antibiotic treatment. Based on these results, we hypothesise that AI-2 plays an important role in controlling colonization and homeostasis of the gut microbiota contributing to the protective properties of these poly-species against pathogens. A synthetic strategy to obtain new beta glycoside analogues of AI-2 that will function as prodrugs to deliver intact AI-2 to the gut, taking advantage of the enzymes that are only produced in the gut, beta-glycosidases, will be presented.
