Synthesis and testing of the first azobenzene mannobioside as photoswitchable ligand for the bacterial lectin FimH

Abstract

SummaryIn order to allow spatial and temporal control of carbohydrate-specific bacterial adhesion, it has become our goal to synthesise azobenzene mannosides as photoswitchable inhibitors of type 1 fimbriae-mediated adhesion of E. coli. An azobenzene mannobioside 2 was prepared and its photochromic properties were investigated. The E→Z isomerisation was found to be highly effective, yielding a long-lived (Z)-isomer. Both isomers, E and Z, show excellent water solubility and were tested as inhibitors of mannoside-specific bacterial adhesion in solution. Their inhibitory potency was found to be equal and almost two orders of magnitude higher than that of the standard inhibitor methyl mannoside. These findings could be rationalised on the basis of computer-aided docking studies. The properties of the new azobenzene mannobioside have qualified this glycoside to be eventually employed on solid support, in order to fabricate photoswitchable adhesive surfaces.

Rational design strategies for FimH antagonists: new drugs on the horizon for urinary tract infection and Crohn’s disease

“…There are also several reports of other biaryl aglycones that contain a spacer between the A and B phenyl rings. For example, Lindhorst created a series of photoactivatable diazo-linked A and B phenyl rings [91-92], and Ernst synthesized mannosides with amide linked A-B rings [86]. …”

Tuning the Effects of Bacterial Membrane Permeability through Photo‐Isomerization of Antimicrobial Cationic Amphiphiles

“…Following previous reports, photo‐isomerization of cationic amphiphiles 2 and 5 was characterized by UV/Vis spectra and by integration of the aromatic regions of their 1 H NMR spectra to quantitatively determine their cis / trans ratios (Section 9, Supporting Information) . The cis / trans ratios of the pre‐irradiated stock solutions of compounds 2 and 5 that were used for the biological assays were quantitatively determined by the integration of their azobenzene aromatic protons (1:99 and 9:91, respectively, Figures S45 and S46 in the Supporting Information).…”

“…[28][29][30] The cis/trans ratios of the pre-irradiated stock solutionso fc ompounds 2 and 5 that were used for the biological assays were quantitativelyd eterminedb yt he integration of their azobenzene aromatic protons (1:99 and Scheme1.Synthesis of photo-isomerizable antimicrobial cationic amphiphiles. [28][29][30] The cis/trans ratios of the pre-irradiated stock solutionso fc ompounds 2 and 5 that were used for the biological assays were quantitativelyd eterminedb yt he integration of their azobenzene aromatic protons (1:99 and Scheme1.Synthesis of photo-isomerizable antimicrobial cationic amphiphiles.…”

Reprint of “Biogenesis and adhesion of type 1 and P pili”

“…Mannosides target the actual adhesin-receptor interaction of type 1 pili, and include mannose based derivatives containing azobenzene, thiazoylamines and long chain alkyl groups [91][92][93]. Orally available diphenyl mannosides have proven effective in combatting established UTIs in vivo [94].…”