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Modulating Lectin Inhibition with N ‐Glycosyl‐1,2,3‐triazole Scaffolds
Author(s) -
Azcune Itxaso,
Balentová Eva,
SagartzazuAizpurua Maialen,
Ignacio Santos J.,
Miranda Jose I.,
Fratila Raluca M.,
Aizpurua Jesus M.
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201201674
Subject(s) - chemistry , moiety , cycloaddition , click chemistry , triazole , docking (animal) , glycosyl , stereochemistry , azide , lectin , combinatorial chemistry , alkyne , dendrimer , fucose , glycan , binding affinities , biochemistry , organic chemistry , receptor , glycoprotein , catalysis , medicine , nursing
The synthesis of three families of sialyl Lewis X (sLe X ) mimetics based on triazole and bis‐triazole scaffolds is reported. The flexibility of these mimetics is dictated by the scaffold and gradually increases from flexible to rigid. All three families were accessible by straightforward synthetic routes and by taking advantage of the unique features and high yields of Cu I ‐catalyzed alkyne–azide cycloaddition (CuAAC) reaction. Glycopeptidomimetics 12 – 15 were submitted to an extensive evaluation of their binding affinities towards fucose‐specific Ulex Europaeus lectin I by using conformational analysis (molecular dynamics), docking calculations, and saturation‐transfer difference (STD) NMR experiments. The results reveal that the recognition of the ligands is mostly dictated by the fucose moiety and that semi‐rigid ligands are better sLe x mimic candidates because their degree of flexibility enables the modulation of their conformation to the best‐fitting position.