Abstract—

Anti-mullerian hormone (AMH), a homodimeric glycoprotein, described over 70 years ago by A. Jost, is the least studied member of the transforming growth factor beta superfamily. Despite the antitumor activity of AMH discovered at the end of the last century, creation of effective AMH-based drugs is hampered primarily by the lack of information on the mechanism of interaction of various AMH forms with a specific type II receptor (MISRII). Previously, we have shown that not only the full-length activated hormone but also its C-terminal fragment (C-rAMH) could bind to MISRII. In this work, using the surface plasmon resonance technique, we have compared the interaction of three forms of recombinant AMH (rAMH) with the MISRII analogue—the chimeric protein MISRII-Fc containing AMH type II receptor and-Fc fragment of the human IgG1 heavy chain. Comparison of the binding of MISRII-Fc, immobilized on a chip with group specificity for human immunoglobulins, to C-rAMH, to intact rAMH (pro-rAMH), and to rAMH containing one uncleaved monomer (hc-rAMH), showed that the K_D of the complexes increased: 1.7 nM, 88 nM and 110 nM, respectively. Thus, we have shown that the C-terminal fragment of AMH exhibits the maximum affinity for the recombinant MISRII analogue, thus indicating the prospects for the development of drugs based on this hormone derivative.

中文翻译：

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不同形式的人重组抗苗勒管激素与 AMH II 型受体嵌合类似物的相互作用研究

摘要——

抗苗勒管激素 (AMH) 是一种同型二聚体糖蛋白，由 A. Jost 于 70 多年前描述，是转化生长因子 β 超家族中研究最少的成员。尽管在上世纪末发现了 AMH 的抗肿瘤活性，但基于 AMH 的有效药物的开发主要受阻，主要是由于缺乏有关各种 AMH 形式与特定 II 型受体 (MISRII) 相互作用机制的信息。以前，我们已经表明，不仅全长激活激素，而且其 C 末端片段 (C-rAMH) 都可以与 MISRII 结合。在这项工作中，我们使用表面等离子体共振技术，比较了三种形式的重组 AMH (rAMH) 与 MISRII 类似物的相互作用——嵌合蛋白 MISRII-Fc 含有 AMH II 型受体和人 IgG1 重链的 Fc 片段。链。复合物的K _D增加：分别为 1.7 nM、88 nM 和 110 nM。因此，我们已经证明 AMH 的 C 端片段对重组 MISRII 类似物表现出最大的亲和力，从而表明基于这种激素衍生物的药物开发前景。