Production of anti-amoxicillin ScFv antibody and simulation studying its molecular recognition mechanism for penicillins
Production of anti-amoxicillin ScFv antibody and simulation studying its molecular recognition mechanism for penicillins
复制标题
抗阿莫西林ScFv抗体的制备及其青霉素分子识别机制的模拟研究
DOI：
10.1080/03601234.2016.1198639
复制
发表时间：
2016-01-01
影响因子：
2
通讯作者：
Li, Yu W.
中科院分区：
文献类型：
--
作者：
Liu, Jing;Zhang, Hui C.;Li, Yu W.
摘要抗体与其半抗原的分子识别机制是一个非常有趣的问题。本研究的目的是研究抗阿莫西林抗体与青霉素类药物的分子间相互作用。单链可变片段（ScFv）抗体由分泌阿莫西林单克隆抗体的杂交瘤细胞株产生。重组ScFv抗体对青霉素类药物的识别能力与亲本单克隆抗体相似，可同时识别11种青霉素类药物，交叉反应率为18- 107%。利用同源模建方法模拟了单链抗体的三维结构，并利用分子对接方法研究了其与11种青霉素的分子间相互作用。结果表明：3个CDR参与抗体识别; CDR L3 Arg 100、CDR H3 Tyr 226和CDR H3 Arg 228是关键的接触氨基酸残基;氢键是抗体与药物分子间的主要作用力;青霉素类药物的核心结构是抗体的主要结合位置。这些结果可以解释抗阿莫西林抗体对阿莫西林及其类似物的识别机制。这是首次报道青霉素单链抗体的制备及其识别机制的研究。
ABSTRACT The molecular recognition mechanism of an antibody for its hapten is very interesting. The objective of this research was to study the intermolecular interactions of an anti-amoxicillin antibody with penicillin drugs. The single chain variable fragment (ScFv) antibody was generated from a hybridoma cell strain excreting the monoclonal antibody for amoxicillin. The recombinant ScFv antibody showed similar recognition ability for penicillins to its parental monoclonal antibody: simultaneous recognizing 11 penicillins with cross-reactivities of 18–107%. The three-dimensional structure of the ScFv antibody was simulated by using homology modeling, and its intermolecular interactions with 11 penicillins were studied by using molecular docking. Results showed that three CDRs are involved in antibody recognition; CDR L3 Arg 100, CDR H3 Tyr226, and CDR H3 Arg 228 were the key contact amino acid residues; hydrogen bonding was the main antibody–drug intermolecular force; and the core structure of penicillin drugs was the main antibody binding position. These results could explain the recognition mechanism of anti-amoxicillin antibody for amoxicillin and its analogs. This is the first study reporting the production of ScFv antibody for penicillins and stimulation studying its recognition mechanism.