In the battle against antibiotic resistance of bacterial pathogens, alternative or complementary approaches need to be explored. One such approach is to block the proteins involved in adhesion and invasion of the pathogen. For the resistance prone<i> P. aeruginosa, </i>the protein LecA is a known virulence factor and involved in adhesion, invasion and also the formation of biofilms. The proteins has binding specificity for glycans terminating in galactose moieties. Two binding sites within the LecA tetramer are separated by a 30 angstrom distance. Such a distance can be bridged with a suitable spacer to enable simultaneous binding to both sites which should result in enhanced binding. We explored rigidified spacers to optimize the potency of divalent binding. The challenge of creating soluble yet well-defined spacers to cover a sizable distance was met with the use of alternating glucose-triazole moieties, directly linked. A high sensitivity of the inhibitory potency vs. the spacer distance was observed, with the most potent low nanomolar ligands. Other systems to be discussed are tetravalent ligands for the pig pathogen <i>Streptococcus suis</i> and tetra- and pentavalent and polymeric ligands for cholera toxin, the causative agent of cholera.

Blocking bacterial toxins and lectins with multivalent carbohydrates

254th National Meeting (2017)

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