Martin, Harlei and Goyard, David and Margalit, Anatte and Doherty, Kyle and Renaudet, Olivier and Kavanagh, Kevin and Velasco-Torrijos, Trinidad (2021) Multivalent Presentations of Glycomimetic Inhibitor of the Adhesion of Fungal Pathogen Candida albicans to Human Buccal Epithelial Cells. Bioconjugate Chemistry, 32 (5). pp. 971-982. ISSN 1043-1802

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Abstract

Candida albicans causes some of the most prevalent hospital-acquired fungal infections, particularly threatening for immunocompromised patients. C. albicans strongly adheres to the surface of epithelial cells so that subsequent colonization and biofilm formation can take place. Divalent galactoside glycomimetic 1 was found to be a potent inhibitor of the adhesion of C. albicans to buccal epithelial cells. In this work, we explore the effect of multivalent presentations of glycomimetic 1 on its ability to inhibit yeast adhesion and biofilm formation. Tetra-, hexa-, and hexadecavalent displays of compound 1 were built on RAFT cyclopeptide- and polylysine-based scaffolds with a highly efficient and modular synthesis. Biological evaluation revealed that the scaffold choice significantly influences the activity of the lower valency conjugates, with compound 16, constructed on a tetravalent polylysine scaffold, found to inhibit the adhesion of C. albicans to human buccal epithelial cells more effectively than the glycomimetic 1; however, the latter performed better in the biofilm reduction assays. Interestingly, the higher valency glycoconjugates did not outperform the anti-adhesion activity of the original compound 1, and no significant effect of the core scaffold could be appreciated. SEM images of C. albicans cells treated with compounds 1, 14, and 16 revealed significant differences in the aggregation patterns of the yeast cells.

Item Type:	Article
Additional Information:	Cite as: Martin, H., Goyard, D., Margalit, A., Doherty, K., Renaudet, O., Kavanagh, K. & Velasco-Torrijos, T. 2021, "Multivalent Presentations of Glycomimetic Inhibitor of the Adhesion of Fungal Pathogen Candida albicans to Human Buccal Epithelial Cells", Bioconjugate chemistry, vol. 32, no. 5, pp. 971-982.
Keywords:	Biofilms;Fungi;Mixtures;Scaffolds;Solutions
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	17321
Identification Number:	https://doi.org/10.1021/acs.bioconjchem.1c00115
Depositing User:	Dr. Kevin Kavanagh
Date Deposited:	15 Jun 2023 08:21
Journal or Publication Title:	Bioconjugate Chemistry
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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