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Abstract
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.
Highlights
Schistosomiasis, a serious disease caused by intravascular trematodes of the genus Schistosoma, is one of the world’s major public health problems [1,2,3,4]
The results show that a novel peptide inhibited SjTGR activity likely by preventing the binding of substrates to SjTGR
Phage was propagated in Escherichia coli strain ER2738 provided with the kit. 3,3’,5,5’-Tetramethylbenzidine (TMB) substrate solution was purchased from Neobioscience Technology Company Limited (Beijing, China) and horseradish peroxidase (HRP) conjugated anti-M13 monoclonal antibody from GE Healthcare Life Sciences (Piscataway, NJ, USA)
Summary
Schistosomiasis, a serious disease caused by intravascular trematodes of the genus Schistosoma, is one of the world’s major public health problems [1,2,3,4]. The drug of choice, praziquantel (PZQ) [6, 7], is administered globally to 100 million people each year; but sensitivity problems are emerging. Artemisinin, which was developed as antimalaria drug, seems to be active against Schistosoma [15]. Juvenile worms are more sensitive to the drug than adult worms [15]. As there is currently no other effective treatment against schistosomiasis, development of new antischistosomal agents to curb the emergence of drug-resistance should be a high priority
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