A self-assembled multivalent pseudopolyrotaxane for binding galectin-1.
A self-assembled pseudopolyrotaxane consisting of lactoside-displaying cyclodextrin (CD) "beads" threaded onto a linear polyviologen "string" was investigated for its ability to inhibit galectin-1-mediated T-cell agglutination. The CDs of the pseudopolyrotaxane are able to spin around the axis of the polymer chain as well as to move back and forth along its backbone to alter the presentation of its ligand. This supramolecular superstructure incorporates all the advantages of polymeric structures, such as the ability to span large distances, along with a distinctively dynamic presentation of its lactoside ligands to afford a neoglycoconjugate that can adjust to the relative stereochemistries of the lectin's binding sites. The pseudopolyrotaxane exhibited a valency-corrected 10-fold enhancement over native lactose in the agglutination assay, which was greater than the enhancements observed for lactoside-bearing trivalent glycoclusters and a lactoside-bearing chitosan polymer tested using the same assay. The experimental results indicate that supramolecular architectures, such as the pseudopolyrotaxane, provide tools for investigating protein-carbohydrate interactions.
Nelson
Alshakim
A
California NanoSystems Institute, Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
Belitsky
Jason M
JM
Vidal
Sébastien
S
Joiner
C Steven
CS
Baum
Linda G
LG
Stoddart
J Fraser
JF
D000372:Agglutination Tests; D002240:Carbohydrate Sequence; D045744:Cell Line, Tumor; D048271:Chitosan / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D037483:Galectin 1 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015458:Leukemia, T-Cell; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology; D043862:Rotaxanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D014755:Viologens / Q000138:chemical synthesis / Q000737:chemistry; D047391:alpha-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology
D037483:Galectin 1; D006027:Glycosides; C445499:LGALS1 protein, human; D011994:Recombinant Proteins; D043862:Rotaxanes; D014755:Viologens; D047391:alpha-Cyclodextrins; C008245:lactosides; D048271:Chitosan