Chemistry Reference
In-Depth Information
FIGURE 16.19
Transfection efficiency and antiprion activity of cationic phosphorus
dendrimers.
cells, depending on the concentration and the generation of the dendrimer
38-G
n
is
shown in Figure 16.19 (right part), by the disappearance of the black bars. The
efficiency of the anti-PrP
Sc
agents is
38-G
4
>
38-G
5
>
38-G
3
. The most efficient
dendrimer (
38-G
4
) was then used against other strains of prions, including Bovine
Spongiform Encephalopathy (“mad cow” disease) and was also found efficient in all
cases. Furthermore, the cured cells show a persistent reduction in the PrP
Sc
levels, and
no transmission of infectivity was observed when the treated cells were used to
“infect” healthy cells. In view of these important preliminary results, dendrimer
38-G
4
was tested with mice infected. Two days after contamination, a series of mice
received an injection of 100
38-G
4
, which was repeated every 2 days for
1 month. The amount of PrP
Sc
detected in the spleen of the treated mice compared to
untreated mice shows a diminishing of 80% of the amount of PrP
Sc
[84]. Recently,
it was shown that dendrimer
gof
m
38-G
4
interact with heparin, and that these interactions
are responsible for the indirect mechanism of inhibiting the fibrils formation by
dendrimers [85].
Besides polycationic dendrimers, polyanionic phosphorus dendrimers were
also shown to possess interesting biological properties. The polyanionic dendrimers
53-G
n
were obtained by reaction of the carboxylic acid end groups of dendrimer
41-G
n
with an aminosugar analog of galactosylceramide. This species forms
spontaneously bilayer vesicles in water by self-assembly [86], and possesses an
anti-HIV activity. Indeed, these compounds were designed as multisite analogs of
galactosylceramide, a glycolipid having a specific affinity for the V3 loop region of
the gp120 viral envelope protein of HIV-1, with the aim of blocking HIV infection
prior the entry of the virus into human cells. Antiviral assays on these supra-
molecular entities (generations 0, 1, and 2), built from either a trifunctional (
53-G
1
,
53-G
2
)orahexafunctionalcore(
53-G
0
,
53-G
1
), have shown the crucial role played
