B. Faroux-corlay et al., Synthesis of single- and double-chain fluorocarbon and hydrocarbon galactosyl amphiphiles and their anti-HIV-1 activity, CARBOHY RES, 327(3), 2000, pp. 223-260
Galactosylceramide (GalCer) is an alternative receptor allowing HIV-1 entry
into CD4(-)/GalCer(+) cells. This glycosphingolipid recognizes the V3 loop
of HIV gp120, which plays a key role in the fusion of the HIV envelope and
cellular membrane. To inhibit HIV uptake and infection, we designed and sy
nthesized analogs of GalCer. These amphiphiles and bolaamphiphiles consist
of single and double hydrocarbon and/or fluorocarbon chain beta-linked to g
alactose and galactosamine. They derive from serine (GalSer), cysteine (Gal
Cys), and ethanolamine (GalAE). The anti-HIV activity and cytotoxicity of t
hese galactolipids were evaluated in vitro on CEM-SS (a CD4(+) cell line),
HT-29, a CD4(-) cell line expressing high levels of GalCer receptor, and/or
HT29 genetically modified to express CD4. GalSer and GalAE derivatives, te
sted in aqueous medium or as part of liposome preparation, showed moderate
anti-HIV-l activities (IC50 in the 20-220 mu M range), whereas none of the
GalCys derivatives was found to be active. Moreover, only some of these ant
i-HIV active analogs inhibited the binding of [H-3]suramin (a polysulfonyl.
compound which displays a high affinity for the V3 loop) to SPC3, a synthe
tic peptide which contains the conserved GPGRAF region of the V3 loop. Our
results most likely indicate that the neutralization of the virion through
masking of this conserved V3 loop region is not the only mechanism involved
in the HIV-1 antiviral activity of our GalCer analogs. (C) 2000 Elsevier S
cience Ltd. All rights reserved.