Covalent Lectin Inhibition and Application in Bacterial Biofilm Imaging

Wagner, Stefanie; Hauck, Dirk; Hoffmann, Michael; Sommer, Roman; Joachim, Ines; Müller, Rolf; Imberty, Anne; Varrot, A.; Titz, Alexander

doi:10.1002/anie.201709368

Cited by 57 publications

(58 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In fact, the largest changes were observed for residues involved in the carbohydrate recognition domain as inferred from galactose binding (Figure , top) . Overall, a consensus of perturbed resonances could be deduced for all of the compounds, suggesting a common binding site (Figure , bottom) …”

Section: Resultsmentioning

confidence: 96%

“…[39] Overall,a consensus ofp erturbed resonances couldb ed educed for all of the compounds, suggesting ac ommon binding site ( Figure 5, bottom). [40] Thus far,p erturbations of the protein resonances have been used to monitort he interactions. Since the incorporation of a fluorine atom offers exquisite possibilities in NMR, we chose to complemento ur studies and to take advantage of this by performing 19 FNMR studies of monofluorinated galactoside derivatives in the presence and absence of LecA ( Figure 6).…”

Section: Biophysical Measurementsmentioning

confidence: 99%

See 1 more Smart Citation

Stereoselective Synthesis of Fluorinated Galactopyranosides as Potential Molecular Probes for Galactophilic Proteins: Assessment of Monofluorogalactoside–LecA Interactions

Denavit

Lainé

Bouzriba

et al. 2019

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

The replacement of hydroxyl groups by fluorine atoms on hexopyranoside scaffolds may allow access to invaluable tools for studying various biochemical processes. As part of ongoing activities toward the preparation of fluorinated carbohydrates, a systematic investigation involving the synthesis and biological evaluation of a series of mono‐ and polyfluorinated galactopyranosides is described. Various monofluorogalactopyranosides, a trifluorinated, and a tetrafluorinated galactopyranoside have been prepared using a Chiron approach. Given the scarcity of these compounds in the literature, in addition to their synthesis, their biological profiles were evaluated. Firstly, the fluorinated compounds were investigated as antiproliferative agents using normal human and mouse cells in comparison with cancerous cells. Most of the fluorinated compounds showed no antiproliferative activity. Secondly, these carbohydrate probes were used as potential inhibitors of galactophilic lectins. The first transverse relaxation‐optimized spectroscopy (TROSY) NMR experiments were performed on these interactions, examining chemical shift perturbations of the backbone resonances of LecA, a virulence factor from Pseudomonas aeruginosa. Moreover, taking advantage of the fluorine atom, the 19F NMR resonances of the monofluorogalactopyranosides were directly monitored in the presence and absence of LecA to assess ligand binding. Lastly, these results were corroborated with the binding potencies of the monofluorinated galactopyranoside derivatives by isothermal titration calorimetry experiments. Analogues with fluorine atoms at C‐3 and C‐4 showed weaker affinities with LecA as compared to those with the fluorine atom at C‐2 or C‐6. This research has focused on the chemical synthesis of “drug‐like” low‐molecular‐weight inhibitors that circumvent drawbacks typically associated with natural oligosaccharides.

show abstract

Section: Resultsmentioning

confidence: 96%

Section: Biophysical Measurementsmentioning

confidence: 99%

Stereoselective Synthesis of Fluorinated Galactopyranosides as Potential Molecular Probes for Galactophilic Proteins: Assessment of Monofluorogalactoside–LecA Interactions

Denavit

Lainé

Bouzriba

et al. 2019

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

show abstract

“…Early attachment may not be a completely random process, but rather may involve preferential attachment to sites that improve the chance of sustaining the development of biofilm [11]. These may involve various adhering chemistries of the external bacterial architecture, such as hydrophilic/hydrophobic attractions from charged amino acids of flagella and pilli, or of carbohydrates and lipids [12][13][14]. However they may occur, biofilms in food manufacturing facilities can lead to contaminated foods, resulting in outbreaks and illnesses among consumers [15].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Commercial Sanitizers Used in Food Processing Facilities for Inactivation of Listeria monocytogenes, E. Coli O157:H7, and Salmonella Biofilms

Aryal

Muriana

2019

Foods

View full text Add to dashboard Cite

Bacteria entrapped in biofilms are a source of recurring problems in food processing environments. We recently developed a robust, 7-day biofilm microplate protocol for creating biofilms with strongly adherent strains of Listeria monocytogenes, Escherichia coli O157:H7, and Salmonella serovars that could be used to examine the effectiveness of various commercial sanitizers. Listeria monocytogenes 99-38, E.coli O157:H7 F4546, and Salmonella Montevideo FSIS 051 were determined from prior studies to be good biofilm formers and could be recovered and enumerated from biofilms following treatment with trypsin. Extended biofilms were generated by cycles of growth and washing daily, for 7 days, to remove planktonic cells. We examined five different sanitizers (three used at two different concentrations) for efficacy against the three pathogenic biofilms. Quaternary ammonium chloride (QAC) and chlorine-based sanitizers were the least effective, showing partial inhibition of the various biofilms within 2 h (1–2 log reduction). The best performing sanitizer across all three pathogens was a combination of modified QAC, hydrogen peroxide, and diacetin which resulted in ~6–7 log reduction, reaching levels below our limit of detection (LOD) within 1–2.5 min. All treatments were performed in triplicate replication and analyzed by one way repeated measures analysis of variance (RM-ANOVA) to determine significant differences (p < 0.05) in the response to sanitizer treatment over time. Analysis of 7-day biofilms by scanning electron microscopy (SEM) suggests the involvement of extracellular polysaccharides with Salmonella and E. coli, which may make their biofilms more impervious to sanitizers than L. monocytogenes.

show abstract

“…Titz and his group are interested in the medicinal chemistry and chemical biology of carbohydrates in physiology and pathobiology. He has reported in ChemistrySelect on two‐step β‐glycoside synthesis, and in Angewandte Chemie on covalent lectin inhibition . Titz is also the winner of the EFMC Prize for a Young Medicinal Chemist in Academia 2018.…”

Section: Awarded …mentioning

confidence: 99%

Robert Foster Cherry Award: N. K. Garg / Innovation Prize in Medicinal/Pharmaceutical Chemistry: F. K. Hansen and A. Titz

2018

Angew Chem Int Ed

View full text Add to dashboard Cite

Covalent Lectin Inhibition and Application in Bacterial Biofilm Imaging

Cited by 57 publications

References 46 publications

Stereoselective Synthesis of Fluorinated Galactopyranosides as Potential Molecular Probes for Galactophilic Proteins: Assessment of Monofluorogalactoside–LecA Interactions

Stereoselective Synthesis of Fluorinated Galactopyranosides as Potential Molecular Probes for Galactophilic Proteins: Assessment of Monofluorogalactoside–LecA Interactions

Efficacy of Commercial Sanitizers Used in Food Processing Facilities for Inactivation of Listeria monocytogenes, E. Coli O157:H7, and Salmonella Biofilms

Robert Foster Cherry Award: N. K. Garg / Innovation Prize in Medicinal/Pharmaceutical Chemistry: F. K. Hansen and A. Titz

Contact Info

Product

Resources

About