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Mannose‐based inhibitors of Escherichia coli adhesion: design and applications (1007.2)
Author(s) -
Bouckaert Julie
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1007.2
Subject(s) - isothermal titration calorimetry , dynamic light scattering , chemistry , glycan , biophysics , structural biology , nanotechnology , materials science , biochemistry , nanoparticle , biology , glycoprotein
Structure‐thermodynamic relationships in protein‐carbohydrate interactions provide important decision makers in the design and maturation of bacterial ant‐adhesives. Many interactions in our innate defense depend on the specific recognition, of a high enough density of a glycan sequence, to evoke immune reaction. Bacteria hijack glycan receptors that are reminiscent of a physiological state of a mamalian cell that indicates a suitable habitat for the completion of their pathogenic cycle. The interruption of this process is envisioned using anti‐adhesives that selectively block bacterial adhesion but do not interfere with the immune system. The understanding of the biophysical basis of host‐pathogen interactions to empower intervention can be studied using purified adhesins and synthetic multivalent inhibitors. We measured affinities and stoichiometries using surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and dynamic light scattering (DLS). The geometry of a multivalent complex was determined using small angle X‐ray scattering (SAXS) and was found to agree with the stoichiometry and molecular size derived from ITC and DLS data respectively. Stunningly, a correlation could be found between the dispersion part of interaction energies (quantum chemical calculations), ITC‐derived entropies and crystal structure electron densities of inhibitors bound to FimH. Grant Funding Source : Supported by ANR‐12‐BSV5‐0016‐01