School of Life Sciences and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu Province 210023, China.
Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu Province 214064, China.
Biomed Res Int. 2018 Jun 5;2018:9483928. doi: 10.1155/2018/9483928. eCollection 2018.
Schistosomiasis is one of the world's major public health problems. Praziquantel is currently the only effective drug against schistosomiasis. As resistance of praziquantel has emerged in some endemic areas, development of new antischistosomal agents should be a high priority. In this study, a phage display peptide library was used for screening for peptide antagonists of thioredoxin glutathione reductase of (SjTGR), which has been identified as an alternative drug target. Three rounds of panning produced four different fusion phages. ELISA proved that all four phages could bind to SjTGR. One peptide, JIPDys1 (aa, WPHNWWPHFKVK), reduced enzyme activity of SjTGR by more than 50%. 2 M of the synthesized peptide of JIPDys1 inhibited the activity of TrxR, GR, and Grx of SjTGR by 32.5%, 100%, and 100%, respectively. The IC values of the synthetic peptide JIPDys1 for TrxR, GR, and Grx were 3.67 M, 0.11 M, and 0.97 M, respectively. Based on computer simulation, it appeared that JIPDys1 binds to the substrate binding sites of glutathione reductase (GR) and glutaredoxin (Grx). Our data show that the peptide, JIPDys1 (aa, WPHNWWPHFKVK), is a promising candidate to develop novel drugs against which acts by binding with SjTGR and reduces enzyme activity of SjTGR.
血吸虫病是全球主要公共卫生问题之一。目前，吡喹酮是唯一有效的抗血吸虫病药物。由于吡喹酮在一些流行地区已经出现耐药性，因此开发新的抗血吸虫药物应该是当务之急。在这项研究中，我们使用噬菌体展示肽库筛选日本血吸虫硫氧还蛋白-谷胱甘肽还原酶（SjTGR）的肽拮抗剂，该酶已被鉴定为替代药物靶点。经过三轮淘选，得到了四个不同的融合噬菌体。ELISA 证明，这四个噬菌体都能与 SjTGR 结合。一种肽，JIPDys1（aa，WPHNWWPHFKVK），使 SjTGR 的酶活性降低了 50%以上。2 M 的合成肽 JIPDys1 分别抑制 SjTGR 的 TrxR、GR 和 Grx 的活性 32.5%、100%和 100%。合成肽 JIPDys1 对 TrxR、GR 和 Grx 的 IC 值分别为 3.67 M、0.11 M 和 0.97 M。基于计算机模拟，JIPDys1 似乎与谷胱甘肽还原酶（GR）和谷氧还蛋白（Grx）的底物结合位点结合。我们的数据表明，肽 JIPDys1（aa，WPHNWWPHFKVK）是一种很有前途的候选药物，可用于开发与 SjTGR 结合并降低其酶活性的新型抗血吸虫药物。
