Identification of Peptide Antagonists to Thioredoxin Glutathione Reductase of Schistosoma japonicum.
Identification of Peptide Antagonists to Thioredoxin Glutathione Reductase of Schistosoma japonicum.
复制标题
日本血吸虫硫氧还蛋白谷胱甘肽还原酶肽拮抗剂的鉴定
DOI：
10.1155/2018/9483928
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发表时间：
2018
影响因子：
--
通讯作者：
Hua ZC
中科院分区：
文献类型：
--
作者：
Song LJ;Li JH;Yin XR;Zhang W;Jin Y;Gao H;Wang J;Yu CX;Hua ZC
血吸虫病是世界上主要的公共卫生问题之一。吡喹酮是目前唯一有效的抗血吸虫病药物。由于吡喹酮的耐药性已经出现在一些流行地区，开发新的抗吡喹酮药物应是一个高度优先事项。在这项研究中，噬菌体展示肽库用于筛选的硫氧还蛋白谷胱甘肽还原酶的日本血吸虫（SjTGR），这已被确定为一个替代的药物靶点的肽拮抗剂。三轮淘选产生四种不同的融合物。ELISA结果表明，4种酶均能与SjTGR结合。一种肽JIPDys1（aa，WPHNWWPHFKVK）使SjTGR的酶活性降低50%以上。2 μM的JIPDys1合成肽对SjTGR的TrxR、GR和Grx活性的抑制率分别为32.5%、100%和100%。合成肽JIPDys1对TrxR、GR和Grx的IC 50值分别为3.67 μM、0.11 μM和0.97 μM。基于计算机模拟，似乎JIPDys1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），是一个有希望的候选人，以开发新的药物抗链球菌。日本血吸虫，其通过与SjTGR结合并降低SjTGR的酶活性而起作用。
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 Schistosoma japonicum (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 μM of the synthesized peptide of JIPDys1 inhibited the activity of TrxR, GR, and Grx of SjTGR by 32.5%, 100%, and 100%, respectively. The IC50 values of the synthetic peptide JIPDys1 for TrxR, GR, and Grx were 3.67 μM, 0.11 μM, and 0.97 μM, 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 S. japonicum which acts by binding with SjTGR and reduces enzyme activity of SjTGR.
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影响因子：
64.8
作者：
Dennis, MS;Eigenbrot, C;Lazarus, RA
通讯作者：
Lazarus, RA
DOI：
10.1590/s0074-02762010000400040
发表时间：
2010-07-01
期刊：
Memórias do Instituto Oswaldo Cruz
影响因子：
--
作者：
Coura, José Rodrigues;Conceição, Maria José
通讯作者：
Conceição, Maria José
影响因子：
1.9
作者：
Guevara-Flores, Alberto;Pablo Pardo, Juan;Rendon, Juan L.
通讯作者：
Rendon, Juan L.
DOI：
10.4269/ajtmh.1996.55.214
发表时间：
1996-08-01
影响因子：
3.3
作者：
Ismail, M;Metwally, A;Bennett, JL
通讯作者：
Bennett, JL
影响因子：
2.9
作者：
Kubas, George;Rees, William;Cortes, Pedro
通讯作者：
Cortes, Pedro