Karolina and Joe’s review article on “Structural considerations for building synthetic glycoconjugates as inhibitors for Pseudomonas aeruginosa lectins” has been published by ChemMedChem. The article is available here: https://doi.org/10.1002/cmdc.202200081

Pseudomonas aeruginosa is a pathogenic bacterium, responsible for a large portion of nosocomial infections globally and designated as critical priority by the World Health Organisation. Its characteristic carbohydrate-binding proteins LecA and LecB, which play a role in biofilm-formation and lung-infection, can be targeted by glycoconjugates. In the review, we present the wide range of inhibitors for these proteins (136 references), highlighting structural features and which impact binding affinity and/or therapeutic effects, including carbohydrate selection; linker length and rigidity; and scaffold topology, particularly for multivalent candidates. We also discuss emerging therapeutic strategies, which build on targeting of LecA and LecB, such as anti-biofilm activity, anti-adhesion and drug-delivery, with promising prospects for medicinal chemistry.

This article would be a good entry-point for any researchers considering tackling P. aeruginosa as a target organism, particularly if they want to build lectin-targeting ligands building on the existing consensus in the field on the best structural features to ensure high lectin affinity.

Thanks to Science Foundation Ireland for funding this research.