Design and synthesis of alpha Gal-conjugated peptide T20 as novel antiviral agent for HIV-immunotargeting.
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.
Institute of Human Virology, University of Maryland Biotechnology Institute, University of Maryland, Baltimore, MD 21201, USA.
Kannan P
KP
Naicker
Hengguang
H
Li
Alonso
A
Heredia
Haijing
H
Song
Lai-Xi
LX
Wang
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002240:Carbohydrate Sequence; D015195:Drug Design; D000077560:Enfuvirtide; D005690:Galactose / Q000737:chemistry*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D008301:Maleimides / Q000737:chemistry; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014312:Trisaccharides / Q000138:chemical synthesis* / Q000737:chemistry
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D007797:Laminin; D008301:Maleimides; D010446:Peptide Fragments; D014312:Trisaccharides; C076569:alpha-galactosyl epitope; D000077560:Enfuvirtide; C043592:maleimide; D005690:Galactose