Multivalent interactions between lectins and supramolecular complexes: Galectin-1 and self-assembled pseudopolyrotaxanes.
Supramolecular 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.
Belitsky
Jason M
JM
California NanoSystems Institute, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Nelson
Alshakim
A
Hernandez
Joseph D
JD
Baum
Linda G
LG
Stoddart
J Fraser
JF
D000372:Agglutination Tests; D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D011232:Chemical Precipitation; D003505:Cyclodextrins / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D037483:Galectin 1 / Q000737:chemistry / Q000378:metabolism*; D006027:Glycosides / Q000737:chemistry; D006801:Humans; D008024:Ligands; D046911:Macromolecular Substances / Q000737:chemistry / Q000494:pharmacology; D008969:Molecular Sequence Data; D020442:Poloxamer / Q000737:chemistry / Q000378:metabolism*; D043862:Rotaxanes / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
D003505:Cyclodextrins; D037483:Galectin 1; D006027:Glycosides; D008024:Ligands; D046911:Macromolecular Substances; D043862:Rotaxanes; C008245:lactosides; C475674:pseudopolyrotaxane; D020442:Poloxamer