Design and synthesis of αGal-conjugated peptide T20 as novel antiviral agent for HIV-immunotargeting
Design and synthesis of αGal-conjugated peptide T20 as novel antiviral agent for HIV-immunotargeting
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DOI：
10.1039/b313844e
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发表时间：
2004-01-01
影响因子：
3.2
通讯作者：
Wang, LX
中科院分区：
文献类型：
--
作者：
Naicker, KP;Li, HG;Wang, LX
描述了一种高效的化学酶合成α gal偶联肽T20作为新型hiv免疫靶向剂。该合成包括化学酶法制备马来酰亚胺功能化的α gal表位及其与肽T20的化学选择性连接。标题化合物包含两个功能域：与人类天然抗gal抗体结合的三糖α gal表位和识别HIV包膜的gp41 n端外结构域的36个氨基酸的gp41肽（T20）。生物学实验表明，合成的偶联物可以很容易地与正常人血清中的天然抗gal抗体（IgG和IgM型）结合，即使在没有人抗体和补体系统的情况下也表现出很强的抗hiv活性。实验数据表明，合成的alphaGal-T20可能通过抗体介导的细胞毒性和/或抗体依赖的补体介导的HIV颗粒和HIV感染细胞的裂解在体内HIV免疫靶向中具有价值，从而为HIV干预提供了额外的维度。
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.