Structural Considerations for Building Synthetic Glycoconjugates as Inhibitors for Pseudomonas aeruginosa Lectins

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.