A Synthetic Galectin Mimic. Issue 29 (15th June 2021)

• Record Type: Journal Article
• Authors: Timmer, Brian J. J.; Kooijman, Arjaan; Schaapkens, Xander; Mooibroek, Tiddo J.
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 29(2021)
• Page Start: 16178
• Page End: 16183
• Publication Date: 2021-06-15
• Subjects: carbohydrate recognition -- carbohydrates -- galactosides -- galectin mimic -- molecular recognition; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202104924
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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 CD2 Cl2 containing 5 % [D6 ]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. Abstract : A synthetic galectin mimic was designed, synthesized, and shown to bind selectively to n ‐octyl‐β‐D‐galactoside.