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

We describe the synthesis together with the results of anti-HIV-l activity and gp120-monolayer binding experiments of new galactosyl amphiphiles, anal ogues of galactosylceramide, an alternative receptor used by HIV to infect CD4 negative cells. These compounds consist of single- and double-chain amp hiphiles containing one or two galactose residues. To favor their clusterin g into galactosyl-rich microdomains, their molecular structure contains als o an amino group or several hydroxyls or anionic groups, such as carboxylat e, sulfate, sulfonate, and phosphate. Among the 12 new galactosylated compo unds reported, a specific anti-HIV activity, although moderate (IC50 from 1 0 to 50 muM), was detected only for three of them, i.e., I-GalSer[CO2Na][C1 4], 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 monolayer s, suggesting that binding of these three derivatives to HIV-1 gp120 may be responsible for their anti-HIV activity.