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A Synthetic Galectin Mimic
Author(s) -
Timmer Brian J. J.,
Kooijman Arjaan,
Schaapkens Xander,
Mooibroek Tiddo J.
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202104924
Subject(s) - galectin , complementarity (molecular biology) , chemistry , residue (chemistry) , galactosides , galactoside , hydrogen bond , stereochemistry , galectin 1 , binding selectivity , biochemistry , molecule , biology , glycoside , organic chemistry , enzyme , immunology , genetics
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.