期刊
ORGANIC & BIOMOLECULAR CHEMISTRY
卷 2, 期 5, 页码 660-664出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/b313844e
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资金
- NIAID NIH HHS [AI54354] Funding Source: Medline
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI054354] Funding Source: NIH RePORTER
An efficient chemo-enzymatic synthesis of alphaGal-conjugated peptide T20 as novel HIV-immuno-targeting agent is described. The synthesis involves chemo-enzymatic preparation of maleimide-functionalized alphaGal epitope and its chemoselective ligation with the peptide T20. The title compound contains two functional domains: the trisaccharide alphaGal 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 alphaGal-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.
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