n-n-dimethylpradimicin-fa-2 and Acquired-Immunodeficiency-Syndrome

The virion surface of the human immunodeficiency virus (HIV-1) is covered with an envelope glycoprotein gp120. Study of the oligosaccharide structures of gp120 suggests that the high mannose type of oligosaccharides are essential for HIV-1 infection. Pradimicin A, an antifungal antibiotic isolated from Actinomadura hibisca, and the derivative BMY-28864 have the ability to inhibit HIV-1 infection in vitro. The inhibitory effect was suppressed by addition of high mannose type oligosaccharides of gp120. BMY-28864 bound directly to gp120, mannose-BSA, and neoglycolipids containing high mannose type oligosaccharides but not to natural mammalian glycoproteins. The binding was Ca2+ dependent and was inhibited by mannose. BMY-28864 is a unique carbohydrate-binding antibiotic which has never been reported. It is possible to block HIV-1 infection by targeting oligosaccharide chains of the envelope glycoprotein.

Topics: Acquired Immunodeficiency Syndrome; Animals; Anthracyclines; Antibiotics, Antineoplastic; Antifungal Agents; Calcium; Carbohydrate Sequence; Drug Design; HIV Envelope Protein gp120; Humans; Molecular Sequence Data; Protein Binding