Synthesis of 1,2,3-triazole-linked galactohybrids and their inhibitory activities on galectins

Abstract

Here a synthesis of novel galactose-1,2,3-triazole conjugates is described. The title compounds were obtained from 3-azido-3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-galactofuranose via a copper catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction. It was demonstrated that the title compounds in their isopropylidene-protected form tend to chelate copper. The copper content can be diminished to 10 ppm by successive treatment with EDTA and Na 2 S followed by chromatographic purification. Acidic hydrolysis of the acetonide protecting groups provided water soluble galactohybrids that were tested for their affinity towards galectin-1 and galectin-3. The trimeric galactohybrid exhibited a 160-fold preference for galectin-3 binding with K d 50 μM. One of the obtained disaccharides was characterized by X-ray analysis.

Low generation polyamine dendrimers bearing flexible tetraethylene glycol as nanocarriers for plasmids and siRNA

“…This procedure has been extensively demonstrated to remove trace amount of copper salt 30 down to the level of <12 ppm. 31 Silica gel column chromatography was performed to isolate the desired compounds.…”

Cu(I)-Catalyzed Click Chemistry in Glycoscience and Their Diverse Applications

“…Turks and co-workers synthesized divalent and multivalent triazolyl galactopyranose glycoconjugates ( 1267 and 1268 ) via CuAAC coupling of 3-azido-3-deoxy-1,2:5,6-di- O -isopropylidene-α- d -galactofuranose with benzene core or glucose core alkynes (Figure ). The developed molecular set exhibited potential Gal-1 and Gal-3 inhibition with appreciable binding affinities. However, the bivalent galactohybrids bearing various linkers and pentavalent galactohybrid had identical binding affinities for the macromolecules.…”

“…Structures of Gal inhibitors constructed as multivalent triazolyl galactopyranose-based conjugates ( 1267 , 1268 ) …”

Multivalent glycosystems for human lectins

“…[210][211][212][213] Some low-valency glycoclusters have been explored as galectin inhibitors. 214,215 Taking into account that Gal-1 is implicated in HIV-1 binding and infectivity of CD4 + T cells, [216][217][218] St-Pierre et al 219 developed a trivalent lactoside derivative that supressed efficiently the Gal-1 mediated HIV-1 infection of host cells. The group of Vidal also explored the avidity of low-valency glycoclusters for Gal-1 by using more sophisticated tetravalent cores, i.e.…”