Glycocalix[4]arenes and their affinity to a library of galectins: the linker matters

Abstract

Galectins are lectins that bind β-galactosides. They are involved in important extra- and intracellular biological processes such as apoptosis, and regulation of the immune system or the cell cycle. High-affinity...

Galectin-targeting glycocalix[4]arenes can enter the cells

“…K D = 952 nM vs. 285 nM. Compound 26 was previously studied using another BLI setup 16 with galectin immobilization on an NTA-type biosensor, and both K D values were comparable ( cf. 285 nM vs. 120 nM).…”

“…15 Our recent study with a simple inhibitor lactose demonstrated that a partial cone glycocalix[4]arene also acts as a strong inhibitor of Gal-3. 16 Generally, glycomimetics are better suited for galectin inhibition than natural carbohydrates due to their biostability and resistance to enzymatic degradation. 17 (Imino)coumaryl glycoconjugates were found to be strong galectin antagonists, 18 and 3- O -coumarylmethyl-disubstituted thiodigalactosides inhibited Gal-1/Gal-3 in a murine model of bleomycin-induced pulmonary fibrosis.…”

“…In addition to efficient inhibition, we show that this novel compound, prepared in a much easier procedure than previously reported for this type of substituents, 23 appropriately balances the hydrophobic character of the resulting glycocalixarene to maximize its cellular association, compared with the lactosyl-decorated counterparts in different valencies. Cone and partial cone conformers, previously proved to be the most efficient for inhibiting Gal-3, 16 were used as the core. The affinity to Gal-3 was determined using our original setup of biolayer interferometry (BLI).…”

“…Calix[4]arene cores 11 , and 12 were prepared by locking the calix[4]arene conformation by alkylation using propyl iodide, 24 followed by ipso -nitration, reduction to amino groups, and coupling with 4-pentynoic acid. 16 Spontaneous inversion of individual rings in the calix[4]arene core is suppressed by rim substituents greater than ethyl. The conformationally mobile calix[4]arenes may bring further increase in affinity to biological targets.…”

“…The extracted equilibrium dissociation constant K D correlated well with respective values from the steady-state results, and its value for lactose also agreed well with previous ELISA results. 16…”