PhD defense: Yu Fan

Title

Synthesis and study of photoswitchable glycoligands targeting Pseudomonas aeruginosa lectins.

Abstract

Pseudomonas aeruginosa is a Gram negative pathogen whose adhesion and biofilm formation involve the lectins LecA and LecB, making them attractive targets for anti-virulence strategies. This thesis aimes to develop azobenzene-based photoswitchable glycoligands targeting both lectins for light-controlled carbohydrate-lectin recognition. A series of water-soluble monovalent O- and S-galactosyl or fucosyl azobenzenes was developed. The ligands exhibit efficient and reversible E/Z photoisomerization with good photo- and thermal stability. Isothermal titration calorimetry studies revealed their micromolar binding affinities towards the corresponding LecA or LecB, with some of them exhibiting 2- to 3-fold differences in affinity between the E and Z isomers. To enhance LecA binding affinity and amplify the affinity difference between the E/Z isomers, two series of divalent symmetric galactoligands bearing relatively rigid linkers such as glucoside (or inositol)-triazole (or amide)-azobenzene-triazole (or amide)-glucoside (or inositol) were developed. These ligands exhibit excellent photophysical properties and enhanced LecA binding affinity of nanomolar to low-nanomolar. A tetra-ortho fluorinated azobenzene derivative showed the largest E/Z affinity difference of approximately 3.5 fold. The diastereomeric mixtures derivated from racemic inositol showd higher affinities than their stereochemically defined counterparts. Furthermore, a few photoswitchable and fluorescent glycoligands have been developed.

PhD supervision

• Director: Pr. Joanne Xie, Professor, PPSM, ENS Paris-Saclay
• Co-director: Dr. Guillaume Laurent, Research Director, PPSM, CNRS

Members of the jury

• Carmen GALAN, Professor, University of Bristol, Reviewer

• Alexander TITZ, Professor, Universität des Saarlandes,, Reviewer

• Anne IMBERTY, Research Director, CNRS - Université Grenoble Alpes, Examiner

• Sébastien VIDAL, Research Director, CNRS - Université Paris-Saclay, Examiner