1. Multivalent Interactions between Lectins and Supramolecular Complexes: Galectin-1 and Self-Assembled Pseudopolyrotaxanes
- Author
-
Alshakim Nelson, Jason M. Belitsky, Joseph D. Hernandez, Linda G. Baum, and J. Fraser Stoddart
- Subjects
Galectin 1 ,Rotaxanes ,Macromolecular Substances ,Stereochemistry ,T-Lymphocytes ,Molecular Sequence Data ,Clinical Biochemistry ,Supramolecular chemistry ,Poloxamer ,Ligands ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Agglutination Tests ,Drug Discovery ,Carbohydrate Conformation ,Chemical Precipitation ,Humans ,Non-covalent interactions ,Glycosides ,Binding site ,Molecular Biology ,Pharmacology ,chemistry.chemical_classification ,Cyclodextrins ,Binding Sites ,Cyclodextrin ,biology ,010405 organic chemistry ,Lectin ,General Medicine ,Combinatorial chemistry ,0104 chemical sciences ,3. Good health ,CHEMBIO ,Carbohydrate Sequence ,chemistry ,biology.protein ,Molecular Medicine ,Carbohydrate conformation ,Dimerization - Abstract
SummarySupramolecular chemistry has been employed to develop flexible and adaptable multivalent neoglycoconjugates for binding galectin-1 (Gal-1). Gal-1, a dimeric lectin with two galactoside-binding sites, regulates cancer progression and immune responses. Self-assembled pseudopolyrotaxanes consisting of lactoside-displaying cyclodextrin (LCD) “beads” threaded onto polyviologen “strings” display mobile ligands as a result of cyclodextrin rotation about, and limited translation along, the polymer chain. The pseudopolyrotaxanes rapidly and efficiently precipitate Gal-1 and provide valency-corrected enhancements of up to 30-fold compared to native lactose and 20-fold over free LCD in a T-cell agglutination assay. A supramolecular statistical effect was observed, wherein the efficacy of Gal-1 inhibition correlates with the number of ligands connected to each other solely through mechanical and noncovalent interactions. Such flexible and adaptable self-assembled pseudopolyrotaxanes show promise for the study of multivalent interactions and targeting of therapeutically relevant lectins.
- Published
- 2007
- Full Text
- View/download PDF