Multivalent Interactions Between Lectins and Supramolecular Complexes: Galectin-1 and Self-Assembled Pseudopolyrotaxanes

Abstract

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.

Publisher

Elsevier (Cell Press)

Publication Date

1-1-2007

Publication Title

Chemistry & Biology

Department

Chemistry and Biochemistry

Document Type

Article

DOI

https://dx.doi.org/10.1016/j.chembiol.2007.09.007

Language

English

Format

text

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