Design and synthesis of alpha Gal-conjugated peptide T20 as novel antiviral agent for HIV-immunotargeting

• Published in: Organic & biomolecular chemistry 2004-03, Vol.2 (5), p.660-664
• Main Authors: Naicker, Kannan P, Li, Hengguang, Heredia, Alonso, Song, Haijing, Wang, Lai-Xi
• Format: Article
• Language: English
• Subjects: Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Carbohydrate Sequence; Drug Design; Galactose - chemistry; HIV Envelope Protein gp41 - chemistry; HIV Envelope Protein gp41 - pharmacology; HIV-1 - chemistry; HIV-1 - drug effects; HIV-1 - immunology; Humans; Laminin - pharmacology; Maleimides - chemistry; Molecular Sequence Data; Monocytes - drug effects; Peptide Fragments - chemical synthesis; Peptide Fragments - chemistry; Peptide Fragments - pharmacology; Trisaccharides - chemical synthesis; Trisaccharides - chemistry
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/b313844e

An efficient chemo-enzymatic synthesis of alpha Gal-conjugated peptide T20 as novel HIV-immuno-targeting agent is described. The synthesis involves chemo-enzymatic preparation of maleimide-functionalized alpha Gal epitope and its chemoselective ligation with the peptide T20. The title compound contains two functional domains: the trisaccharide alpha Gal epitope that binds to human natural anti-Gal antibodies and the 36-amino acid gp41 peptide (T20) that recognizes the gp41 N-terminal ectodomain of the HIV envelope. Biological assays demonstrated that the synthetic conjugate could readily bind to natural anti-Gal antibodies (both IgG and IgM type) in normal human serum and exhibited potent anti-HIV activity even in the absence of human antibodies and complement system. The experimental data suggest that the synthetic alpha Gal-T20 might be valuable for in vivo HIV-immuno-targeting via antibody-mediated cytotoxicity and/or antibody-dependent, complement-mediated lysis of HIV particles and HIV-infected cells, thus providing an additional dimension of HIV intervention.