MECHANISM OF ANTI-HIV ACTIVITY OF NEGATIVELY CHARGED ALBUMINS - BIOMOLECULAR INTERACTION WITH THE HIV-1 ENVELOPE PROTEIN GP120

A novel class of polyanionic proteins with potent anti-human immunodef iciency virus type 1 activity, the negatively charged albumins (NCAs), have been reported previously. In vitro antiviral assays established that these compounds preferentially inhibit virus-cell fusion and sync ytium formation and that virus-cell binding is less affected. Here the interaction of the NCAs with synthetic peptides composed of 15-36 ami no acids and corresponding to different parts of the gp120 envelope pr otein is described. Among the gp120 peptides tested, binding of the NC As was observed only with the so-called V3 loop (amino acids 296-330) and the C-terminal part of gp120. A higher number of negatively charge d residues in the albumins resulted in higher binding affinities. NCAs in which, in addition to negative charges, up to 7 or 14 lactose or m annose groups were introduced, respectively, did not exhibit increasin g binding affinity. In contrast, mannosylated albumin containing about 14 mannose groups showed an increased binding compared with native al bumin. Binding of the NCAs to the V3 and C-terminal oligopeptide was c ompetitively inhibited by sulfated polysaccharide heparin and dextran sulfate. This finding indicates that the binding between the gp120 pep tides and the NCAs is likely caused by electrostatic interactions. How ever, the fact that the dissociation constants of dextran sulfate and heparin are orders of magnitude larger compared with the NCAs indicate s that the spatial structure of the proteins and/or hydrophobic intera ctions between the NCAs and the envelope protein may also be involved.