Click multivalent neoglycoconjugates as synthetic activators in cell adhesion and stimulation of monocyte/machrophage cell lines

Abstract

The efficient synthesis of fluorescent and non-fluorescent multivalent neoglycoconjugates is described by means of the Cu(i) catalyzed azide-alkyne 1,3-dipolar cycloaddition ("click-chemistry"). A well-defined glycopolymer, glycocyclodextrin or glycocluster architecture displaying galactose or lactose epitopes has been chosen. Cellular assays using U-937 and RAW 264.7 monocyte/macrophage cells showed that these glycocompounds have the capability to act as synthetic activators mimicking the lipopolysaccharide (LPS) effects. Thus, the click compounds promote cell adhesion and stimulation of monocytes, measured as an increase in the amount of TNFalpha, facilitating their differentiation to macrophages.

Cyclodextrin-based multivalent glycodisplays: covalent and supramolecular conjugates to assess carbohydrate–protein interactions

“…112 The availability of per-(O-2)-propargylbCD was also exploited by Santoyo-Gonzalez and co-workers to prepare skirt-type triazol-linked bGal and bLac heptavalent conjugates through CuAAC using the azide-armed glycosides. 107 …”

“…The method was also applied to the preparation of homogeneous heptavalent glycoclusters. 107 Scheme 21 Click-coupling synthetic step to obtain triazolalkyl-spaced heptavalent glycosidase inhibitors.…”

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

“…The obtained dimeric structures are characterized by an extended bis(1,2,3-triazol-4-yl)linker. The linear alkadiynes (entries 1-4, Table 1) are commercially available, but other precursors of the linkers (1,2-bis(propargyloxy)ethane, 25 2,2-dipropargyl dimedone (4a), 26 5,5-dipropargyl Meldrum's acid (4b) 27 and 5,5-dipropargyl barbituric acid (5) 25 6a-e (see Table 1 Similarly, a combination of 1,3,5-triethynylbenzene (7) and penta-O-propargyl-β-D-glucose (9) 28 with a minimal excess of azidosugar 2 gave trivalent and pentavalent galacto-clusters 8 and 10 in 74 and 61% yields, respectively (Scheme 2).…”

Click Chemistry: A Powerful Tool to Create Polymer‐Based Macromolecular Chimeras

“…Furthermore, fluorescent and non-fluorescent multivalent neoglycoconjugates which were recently prepared by means of Cu(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition were subjected to cellular assays using U-937 and RAW 264.7 monocyte/macrophage cells and showed to possess the ability to act as synthetic activators mimicking the lipopolysaccharide (LPS) effects. [96] The click compounds proved to promote cell adhesion and stimulation of monocytes, as measured from increase in the amount of TNFa, facilitating their differentiation to macrophages. Considering the flexibility and efficiency of ''click chemistry,'' the authors suggest that these well-defined and custom-made click multivalent neoglycoconjugates will be valuable compounds in applications not limited to the activation of monocytes/macrophages but also with potential for the development of therapeutics.…”