Joe Graduations, news, Team

Karolina defends her PhD thesis

Very proud of my very first PhD student Karolina Wojtczak who successfully defended her thesis last Thursday. A lot of hard work has paid off and she has left the group lots of interesting starting points for future projects (in addition to a few more imminent publications). Her thesis was titled “Metal-based glycoconjugates as molecular sensors for lectins and anti-adhesives”.

Karol was an absolute pleasure to have in my lab and I wish her all the best with her bright future. I’m sure she will achieve great things. Congratulations!

A great celebration was had in Galway to mark the occasion.

Thanks to Research Ireland (formerly SFI) (18/SIRG/5501) for financial support and Paul Murphy for co-supervising her, particularly after I moved to UCD last year.

Karol has already started a position as a Development Chemist in Sterling Pharma Solutions.

Joe Publications

ChemComm: Terbium-based lectin sensors

Congratulations to Karolina on her first article published in Chemical Communications. The article has been included in the HOT Articles 2023 Collection as well as a themed collection on Chemosensors and Molecular Logic (related to last year’s MSMLG Conference). The work was considered exciting by the editors and so was featured on the Front Cover of the journal issue.

We describe glycoconjugate terbium(III) complexes, which are able to detect carbohydrate-binding proteins in aqueous buffer solution. When the carbohydrate motif on the complex matches the target of the protein, an enhancement in lanthanide luminescence is observed. The bacterial lectin LecA (from P. aeruginosa) is one of the detected proteins.

Sensing behaviour of complexes Tb.3. See article for full description of results

This work was funded by Science Foundation Ireland (18/SIRG/5501), with support from a 4th year project student, and our collaborators in TU Dublin (Gordon Cooke) and University of Saarland (Alexander Titz, HZI/HIPS). The interdisciplinary work includes synthesis of new sensor molecules, biological assessment and examination of their lectin binding affinity. We believe this work could lead to the development of tools which could use detection of characteristic proteins from pathogens as a means for diagnosis, and hope to follow up on this in future publications.

Joe Publications

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.