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A Synthetic Galectin Mimic

Galectins are a galactoside specific subclass of carbohydrate binding proteins (lectins) involved in various cellular activities, certain cancers, infections, inflammations, and many other biological processes. The molecular basis for the selectivity of galectins is well‐documented and revolves arou...

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Detalles Bibliográficos
Autores principales: Timmer, Brian J. J., Kooijman, Arjaan, Schaapkens, Xander, Mooibroek, Tiddo J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361779/
https://www.ncbi.nlm.nih.gov/pubmed/33964110
http://dx.doi.org/10.1002/anie.202104924
Descripción
Sumario:Galectins are a galactoside specific subclass of carbohydrate binding proteins (lectins) involved in various cellular activities, certain cancers, infections, inflammations, and many other biological processes. The molecular basis for the selectivity of galectins is well‐documented and revolves around appropriate interaction complementarity: an aromatic residue for C−H⋅⋅⋅π interactions and polar residues for (charge assisted) hydrogen bonds with the axial hydroxyl group of a galactoside. However, no synthetic mimics are currently available. We now report on the design and synthesis of the first galectin mimic (6), and show that it has a higher than 65‐fold preference for n‐octyl‐β‐galactoside (8) over n‐octyl‐β‐glucoside (7) in CD(2)Cl(2) containing 5 % [D(6)]DMSO (with K (a)≥4500 M(−1) for 6:8). Molecular modeling informed by nOe studies reveal a high degree of interaction complementarity between 6 and galactoside 8, which is very similar to the interaction complementarity found in natural galectins.