Amphiphilic anionic analogues of galactosylceramide: synthesis, anti-HIV-1 activity, and gp120 binding.

We describe the synthesis together with the results of anti-HIV-1 activity and gp120-monolayer binding experiments of new galactosyl amphiphiles, analogues of galactosylceramide, an alternative receptor used by HIV to infect CD4 negative cells. These compounds consist of single- and double-chain amphiphiles containing one or two galactose residues. To favor their clustering into galactosyl-rich microdomains, their molecular structure contains also an amino group or several hydroxyls or anionic groups, such as carboxylate, sulfate, sulfonate, and phosphate. Among the 12 new galactosylated compounds reported, a specific anti-HIV activity, although moderate (IC(50) from 10 to 50 microM), was detected only for three of them, i.e., I-GalSer[CO2Na][C14], II-GalSer[C14][C7SO3Na], and II-GalSer[C2SO4Na][C14], which contain an anionic group. The marked increase of surface pressure which was observed upon addition of gp120 into the aqueous subphase underneath the monolayers containing these galactolipids indicated gp120 insertion into the monolayers, suggesting that binding of these three derivatives to HIV-1 gp120 may be responsible for their anti-HIV activity.