Pseudosaccharide Functionalized Dendrimers as Potent Inhibitors of DC-SIGN Dependent Ebola Pseudotyped Viral Infection

Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection

“…After 8 hours of incubation at 37º C with 5% CO2, medium on transfection plates was changed to 10 ml DMEM and once again one day after transfection to 7 ml DMEM. Transfection supernatants were harvested after 48 h, centrifuged at 1200 rpm for 10 minutes at RT to remove cell debris, and stored frozen at -80° C. 33,36 …”

Glycodendritic structures: tools to interact with DC-SIGN

“…In these experiments, the tetravalent FIGURE 7 -Structure of tetravalent glycodendrons 3 and 4 and glycodendrimers 5 and 6. systems 3 and 4 were very active in the low micromolar range, and the multivalent systems 5 and 6 showed a very strong inhibition effect with IC 50 in the nanomolar range (Luczkowiak et al, 2011).…”

“…Also, it was introduced for the first time the biological activity of these compounds in a cellular infection model providing important information about the potential use of these new glycomimetics as viral inhibitors. These glycodendrofullerenes act as antiviral agents in a DC-SIGN dependent Ebola pseudotype infection model (Luczkowiak et al, 2013). Glycofullerene with 12 mannoses showed an IC 50 of 2 mM, a very promising data; however, an unexpected result was obtained for the activity of the glycodendrofullerene with 36 mannoses.…”

Carbohydrate Mimics and Lectins: A Source of New Drugs and Therapeutic Opportunities

“…However, appropriate levels of affinity have been obtained when the ligands were presented in a multimeric form. 46,47 The multimeric presentation of the glycomimetics 1 and 2 were synthesized by conjugation of the monovalent ligands to tetra-and multivalent scaffolds based on bishydroxymethylpropionic acid as building block. Tetravalent presentation of the pseudotrisaccharide 2 in dendron 3 (Figure 2) was shown to inhibit trans infection of T lymphocytes by DC-SIGN expressing B-cells, which had been pre-incubated with HIV in the presence of 3.…”

“…Additionally, other multivalent compounds were synthesized to obtain multivalent glycomimetics conjugates with 4-32 copies of the ligands on the surface (3-6, Figure 2) These tetra-and multivalent systems were tested in vitro using an infection model based on pseudotyped viral particles with the Ebola virus envelope glycoprotein GP1. 47 This infection model is exclusively dependent of DC-SIGN. 48 In these experiments, the tetravalent systems 3 and 4 were very active in the low micromolar range, and the multivalent systems G 3 (pseudosugar) 32 showed a very strong inhibition effect with IC50 in the nanomolar range.…”