摘要
目的筛选靶向免疫球蛋白E(IgE)重链可结晶(Fc)段的潜在拮抗药物并评价其拮抗效果。方法采用表面等离子体共振(SPR)技术,从美国食品和药物管理局批准的药物库中高通量筛选出与人重组IgE的Fc段(rhIgE-Fc,500、250、125、62.5、31.3 nmol/L)结合的药物。模拟候选药物与rhIgE蛋白的分子对接模型,采用间接竞争性酶联免疫吸附试验法评估不同候选药物对rhIgE的拮抗效果。结果筛选出3个与rhIgE-Fc段蛋白结合力强的药物,分别为穿心莲内酯琥珀酸钾盐、匹维溴铵和硫辛酸,三者结合力与rhIgE-Fc段蛋白浓度呈正相关。分子对接结果显示,3种候选药物均能有效占据rhIgE蛋白的Fc段结合口袋,分子对接结合能分别为-6.0,-5.3,-4.4 kcal/mol;与目前临床常用的IgE单克隆抗体奥马珠单抗(120µg/mL时拮抗rhIgE效果31.57%)相比,达到同等拮抗效果时穿心莲内酯琥珀酸钾盐、匹维溴铵和硫辛酸所需质量浓度分别为86.04,60.86,167.23 ng/mL。结论穿心莲内酯琥珀酸钾盐、匹维溴铵和硫辛酸可作为潜在的IgE拮抗药物应用于急性过敏和慢性炎性变态反应疾病的治疗。
Objective To screen potential antagonistic drugs targeting immunoglobulin E(IgE)heavy chain Fc fragment,and evaluate their antagonistic effects.Methods Surface plasmon resonance(SPR)technology was used to perform high-throughput screening for drugs from the U.S.Food and Drug Administration approved drug library that bind to the recombinant human IgE Fc fragment(rhIgE-Fc,500,250,125,62.5,and 31.3 nmol/L).Molecular docking models of candidate drugs with the rhIgE protein were simulated,and the antagonistic effects of the candidate drugs against rhIgE were evaluated by indirect competitive enzyme-linked immunosorbent assay.Results Three drugs with strong binding affinity to the rhIgE-Fc fragment protein were identified:potassium andrographolide succinate,pinaverium bromide,and lipoic acid.The binding affinities of these three drugs were positively correlated with the concentration of the rhIgE-Fc fragment protein.Molecular docking results showed that all three candidate drugs effectively occupied the Fc fragment binding pocket of the rhIgE fragment protein,with molecular docking binding energies of−6.0,−5.3,and−4.4 kcal/mol,respectively.Compared with the currently clinically used IgE monoclonal antibody omalizumab(which exhibited a 31.57%antagonistic effect against rhIgE at 120μg/mL),the mass concentrations required for potassium andrographolide succinate,pinaverium bromide,and lipoic acid to achieve an equivalent antagonistic effect were 86.04,60.86,and 167.23 ng/mL,respectively.Conclusion Potassium andrographolide succinate,pinaverium bromide,and lipoic acid can be used as potential IgE antagonist drugs for the treatment of acute allergic and chronic inflammatory allergic diseases.
作者
唐蕾
王海
张颖宜
张转铃
黄艳
TANG Lei;WANG Hai;ZHANG Yingyi;ZHANG Zhuanling;HUANG Yan(Guangzhou Chuangrui Health Technology Co.,Ltd.,Guangzhou,Guangdong 511466,China;Key Laboratory of Tropical Disease Control,Ministry of Education,Sun Yat-sen University,Guangzhou,Guangdong 510080,China;School of Public Health,Sun Yat-sen University,Guangzhou,Guangdong 510080,China;Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,Guangdong 510080,China)
出处
《中国药业》
2026年第8期38-43,共6页
China Pharmaceuticals
基金
广东省基础与应用基础研究基金项目[2023A1515140139]。
