日本血吸虫抗氧化靶标蛋白SjTGR多肽抑制剂的筛选及其相互作用机制研究

Schistosoma japonicum is a parasitic disease affecting millions of people in China. Current treatment relies on a single drug of praziquantel, however, therapy is at risky because of the high probability to cause resistance. This study focus on the antioxidant proteins of SjTGR (Thioredoxin Glutathione Reductase from Schistosoma Japonicum), which has been reported as the drug targets for antischistosomal therapy. The peptide inhibitors will be designed and screened by using surface plasmon resonance and scanning probe microscopy as main research techniques. The screen system will be constructed for peptide inhibitors to the targets of SjTGR proteins. We also will investigate the mechanism of interaction between peptide inhibitors and SjTGR proteins. Finally, the application of peptide inhibitors as chemical medicines for Schistosoma japonicum will be explored. These results will be probably lay a solid foundation for development of chemical drugs with high affinity and specificity.

日本血吸虫病是严重危害我国人民生命健康的感染性疾病。吡喹酮是针对血吸虫病有效的化疗药物，但目前由于该药物的大量重复使用而产生了抗药性。本研究选取血吸虫抗氧化靶标蛋白-日本血吸虫硫氧还蛋白过氧化物酶（SjTGR）为研究对象，针对其序列结构设计并筛选出可能对SjTGR具有抑制活性的多肽，利用表面等离子体共振检测仪和扫描探针显微镜为主要手段，建立以靶标蛋白酶为目标的多肽抑制剂筛选体系，阐明其与多肽抑制剂的作用机制；探索多肽抑制剂作为化学治疗药物在抗日本血吸虫病上的用途。该研究将为发现具备高亲和性与强特异性的抗血吸虫病化学治疗新型药物打下坚实的基础。

本项目中针对血吸虫防治药物出现抗药性问题，选取血吸虫抗氧化靶标蛋白（日本血吸虫硫氧还蛋白过氧化物酶）为靶标，通过计算机辅助设计法设计了一系列多肽抑制剂。运用SPR技术、噬菌体展示技术和体外活性测试酶活性实验筛选了多肽抑制剂，在此基础上采用血吸虫成虫来评价抑制剂杀灭效果，最终获得多个具有良好杀虫效果的抑制剂。该研究将为设计具备高亲和性与强特异性的抗血吸虫病化学治疗新型药物打下坚实的基础。