Structural Considerations for Building Synthetic Glycoconjugates as Inhibitors for Pseudomonas aeruginosa Lectins |
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Authors: | Karolina Wojtczak Dr Joseph P Byrne |
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Affiliation: | School of Biological and Chemical Sciences, National University of Ireland Galway, University Road, Galway, Ireland |
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Abstract: | 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. Here we review 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. |
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Keywords: | carbohydrate-protein interactions glycoconjugates lectins Pseudomonas aeruginosa biofilms |
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