Article on lectin-inhibitors published in ChemMedChem

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.

New article in RSC Advances: Glycoclusters with anti-biofilm activity

Our new article, published in RSC Advances (a Gold Open Access journal), describes a series of new ruthenium-centred glycoclusters, which present four carbohydrate motifs around a three-dimensional octahedral scaffold. Multivalent glycoclusters have previously shown the ability to inhibit the carbohydrate-binding proteins which are produced by bacterium P. aeruginosa. Gordon Cooke’s group in TU Dublin tested these new compounds for their ability to inhibit growth of biofilm by P. aeruginosa and we observed that complex 8Gal, with flexible arms between the scaffold core and the galactose motif gave up to 80% inhibition of biofilm, when compared to the control – the other complexes and the ligand did not show antimicrobial activity. We propose that this activity is due to the ability of galactose to interact with the carbohydrate-binding protein LecA.

We thank Science Foundation Ireland for financial support for this work, as well as UCD School of Medicine’s SSRA Scheme, where preliminary studies began.

Walk for Cystic Fibrosis Ireland

Joe raised funds for Cystic Fibrosis Ireland by taking part in their annual Head2Head walk around Dublin Bay. Our research aims to develop diagnostic tools that could speed up diagnosis of P. aeruginosa infections, a widespread problem for people with CF – it seemed only right to try to raise some funds for organisations supporting people with the disease. Thanks to everyone who donated!

Joe in Sandymount starting his walk. The destination is at the end of the headland just next to his left ear!