Biophysical and structural characterization of mono/di-arylated lactosamine derivatives interaction with human galectin-3

Combination of biophysical and structural techniques allowed characterizing and uncovering the mechanisms underlying increased binding affinity of lactosamine derivatives for galectin 3. In particular, complementing information gathered from X-ray crystallography, native mass spectrometry and isothe...

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Veröffentlicht in:Biochemical and biophysical research communications 2017-07, Vol.489 (3), p.281-286
Hauptverfasser: Atmanene, Cédric, Ronin, Céline, Téletchéa, Stéphane, Gautier, François-Moana, Djedaïni-Pilard, Florence, Ciesielski, Fabrice, Vivat, Valérie, Grandjean, Cyrille
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Sprache:eng
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Zusammenfassung:Combination of biophysical and structural techniques allowed characterizing and uncovering the mechanisms underlying increased binding affinity of lactosamine derivatives for galectin 3. In particular, complementing information gathered from X-ray crystallography, native mass spectrometry and isothermal microcalorimetry showed favorable enthalpic contribution of cation-π interaction between lactosamine aryl substitutions and arginine residues from the carbohydrate recognition domain, which resulted in two log increase in compound binding affinity. This incrementing strategy allowed individual contribution of galectin inhibitor moieties to be dissected. Altogether, our results suggest that core and substituents of these saccharide-based inhibitors can be optimized separately, providing valuable tools to study the role of galectins in diseases. [Display omitted] •X-ray structures of the galectin-3 CRD solved with type II lactosamine inhibitors.•Binding affinities determined by native mass spectrometry and isothermal calorimetry.•Affinity consistently increases with the number of aromatic substituents.•Enhanced affinity results from cation-π interactions, which can be cumulated.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2017.05.150