Chemotherapy of an experimental Trypanosoma cruzi infection with specific immunoglobulin-chlorambucil conjugate.

Chemotherapy of an experimental Trypanosoma cruzi infection with specific immunoglobulin-chlorambucil conjugate.
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使用特异性免疫球蛋白-苯丁酸氮芥结合物对实验性克氏锥虫感染进行化疗。

DOI:
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发表时间:
1998
期刊:
Laboratory investigation; a journal of technical methods and pathology
影响因子:
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通讯作者:
A. Teixeira
A. Teixeira
中科院分区:
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文献类型:
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作者:
M. S. Carvalhaes;J. Santana;O. T. Nóbrega;J. B. Aragão;P. Grellier;J. Schrével;A. Teixeira

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杂交分子构建与克氏锥虫抗原的多克隆抗体或单克隆抗体对布氏锥虫低密度脂蛋白(LDL)受体与苯丁酸氮芥共轭。杂交分子的物理化学分析显示,每个IgG中有四个苯丁酸氮芥偶联位点,结合常数约为10(4)。IgG完整性的维持由其圆二色性图案指示。该杂合分子的生物活性通过其对寄生虫的移动和增殖的抑制作用来证明。IgG-苯丁酸氮芥偶联物,用抗T. B.布氏低密度脂蛋白受体,导致T. cruzi形成,尽管其水平比用小鼠多克隆抗T.与药物相关的cruzi IgG。针对实验T.用特异性IgG-苯丁酸氮芥缀合物感染克氏杆菌导致寄生虫血症和死亡率的持续降低,从而显示其在控制该疾病的急性形式中的潜在有用性。
Hybrid molecules were constructed with either polyclonal antibodies against Trypanosoma cruzi antigens or monoclonal antibody against Trypanosoma brucei brucei low-density lipoprotein (LDL)-receptor conjugated with chlorambucil. Physical-chemical analysis of the hybrid molecule showed four chlorambucil coupling sites in each IgG and a binding constant in the order of 10(4). Maintenance of IgG integrity was indicated by its circular dichroism pattern. Biologic activity of the hybrid molecule was shown by its inhibitory effect on the mobility and proliferation of the parasite. An IgG-chlorambucil conjugate, produced with monoclonal antibody anti-T. b. brucei LDL-receptor, led to the immobilization of the T. cruzi forms, albeit at a much lesser level than that obtained with a mouse polyclonal anti-T. cruzi IgG linked to the drug. Targeting experimental T. cruzi infection with a specific IgG-chlorambucil conjugate resulted in consistent reduction of parasitemia and mortality, thus showing its potential usefulness in controlling the acute form of the disease.