Martin, Harlei and Masterson, Hannah and Kavanagh, Kevin and Velasco-Torrijos, Trinidad (2021) The Synthesis and Evaluation of Multivalent Glycopeptoids as Inhibitors of the Adhesion of Candida albicans. Pathogens, 10 (5). p. 572. ISSN 2076-0817

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Abstract

: Multivalency is a strategy commonly used by medicinal carbohydrate chemists to increase the affinity of carbohydrate-based small molecules for their protein targets. Although this approach has been very successful in enhancing binding to isolated carbohydrate-binding proteins, anticipating the multivalent presentations that will improve biological activity in cellular assays remains challenging. In this work we investigate linear molecular scaffolds for the synthesis of a low valency presentation of a divalent galactoside 1, previously identified by us as an inhibitor of the adhesion of opportunistic fungal pathogen Candida albicans to buccal epithelial cells (BECs). Adhesion inhibition assays revealed that multivalent glycoconjugate 3 is more effective at blocking C. albicans adherence to BECs upon initial exposure to epithelial cells. Interestingly, 3 did not seem to have any effect when it was pre-incubated with yeast cells, in contrast to the original lead compound 1, which caused a 25% reduction of adhesion. In competition assays, where yeast cells and BECs were co-incubated, multivalent glycoconjugate 3 inhibited up to 49% C. albicans adherence in a dose-dependent manner. The combined effect of compound 1 towards both yeast cells and BECs allowed it to achieve over 60% inhibition of the adhesion of C. albicans to BECs in competition assays

Item Type:	Article
Additional Information:	Cite as: Martin, H., Masterson, H., Kavanagh, K. & Velasco-Torrijos, T. 2021, "The Synthesis and Evaluation of Multivalent Glycopeptoids as Inhibitors of the Adhesion of Candida albicans", Pathogens (Basel), vol. 10, no. 5, pp. 572.
Keywords:	multivalency; anti-adhesion glycoconjugates; antifungal agents; Candida albicans; glycomimetics
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	17322
Identification Number:	https://doi.org/10.3390/pathogens10050572
Depositing User:	Dr. Kevin Kavanagh
Date Deposited:	15 Jun 2023 09:21
Journal or Publication Title:	Pathogens
Publisher:	MDPI
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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