TY - JOUR
T1 - Multivalent Interactions between Lectins and Supramolecular Complexes
T2 - Galectin-1 and Self-Assembled Pseudopolyrotaxanes
AU - Belitsky, Jason M.
AU - Nelson, Alshakim
AU - Hernandez, Joseph D.
AU - Baum, Linda G.
AU - Stoddart, J. Fraser
N1 - Funding Information:
This work was supported by the National Institutes of Health (GM63281) and the National Science Foundation (CHE-9974928). J.M.B. is grateful to the National Institutes of Health for the award of a postdoctoral fellowship.
PY - 2007/10/26
Y1 - 2007/10/26
N2 - 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.
AB - 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.
KW - CHEMBIO
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U2 - 10.1016/j.chembiol.2007.09.007
DO - 10.1016/j.chembiol.2007.09.007
M3 - Article
C2 - 17961826
AN - SCOPUS:35349011634
SN - 1074-5521
VL - 14
SP - 1140
EP - 1151
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 10
ER -
