Monoclonal antibodies (mAbs) against morphine are important in the development of immunotherapeutic and diagnostic methods for the treatment and prevention of drug addiction. By the surface plasmon resonance (SPR) and enzyme immunoassay techniques, we characterized two previously obtained mAbs 3K11 and 6G1 and showed their ability to recognize free morphine and morphine‐containing antigens in different ways because of the epitope specificity thereof. Using the defined amino acid sequences, we obtained three‐dimensional models of the variable regions of Fab fragments of these antibodies and compared them with the known sequence and spatial structure of the anti‐morphine antibody 9B1. Docking simulations are performed to obtain models of the antibodies complexes with morphine. Differences in the models of 3K11 and 6G1 complexes with morphine correlate with their experimentally detected epitope specificity. The results, in particular, can be used for the structure‐based design of the corresponding humanized antibodies. According to our modeling and docking results, the very different modes of morphine binding to mAbs 3K11 and 6G1 are qualitatively similar to those previously reported for cocaine and two anti‐cocaine antibodies. Thus, the obtained structural information brings more insight into the hapten recognition diversity.

中文翻译：

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两种抗吗啡单克隆抗体的表位特异性：体外和计算机研究。

针对吗啡的单克隆抗体 (mAb) 在开发用于治疗和预防毒瘾的免疫治疗和诊断方法中很重要。通过表面等离子共振 (SPR) 和酶免疫分析技术，我们表征了两种先前获得的 mAb 3K11 和 6G1，并且由于其表位特异性，显示了它们以不同方式识别游离吗啡和含吗啡抗原的能力。使用定义的氨基酸序列，我们获得了这些抗体 Fab 片段可变区的三维模型，并将它们与抗吗啡抗体 9B1 的已知序列和空间结构进行了比较。进行对接模拟以获得抗体与吗啡复合物的模型。具有吗啡的 3K11 和 6G1 复合物模型的差异与其实验检测到的表位特异性相关。该结果尤其可用于相应人源化抗体的基于结构的设计。根据我们的建模和对接结果，吗啡与 mAb 3K11 和 6G1 结合的非常不同的模式在性质上与先前报道的可卡因和两种抗可卡因抗体相似。因此，获得的结构信息可以更深入地了解半抗原识别的多样性。吗啡与 mAb 3K11 和 6G1 结合的非常不同的模式与先前报道的可卡因和两种抗可卡因抗体在性质上相似。因此，获得的结构信息可以更深入地了解半抗原识别的多样性。吗啡与 mAb 3K11 和 6G1 结合的非常不同的模式与先前报道的可卡因和两种抗可卡因抗体在性质上相似。因此，获得的结构信息可以更深入地了解半抗原识别的多样性。