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首页> 外文期刊>Parasitology >Oligopeptidase B and B2: comparative modelling and virtual screening as searching tools for new antileishmanial compounds
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Oligopeptidase B and B2: comparative modelling and virtual screening as searching tools for new antileishmanial compounds

机译：寡肽酶B和B2：对比较建模和虚拟筛选作为新的抗恋盲目化合物的搜索工具

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摘要

Leishmaniasis are diseases caused by parasites of the genus Leishmania and transmitted to humans by the bite of infected insects of the subfamily Phlebotominae. Current drug therapy shows high toxicity and severe adverse effects. Recently, two oligopeptidases (OPBs) were identified in Leishmania amazonensis, namely oligopeptidase B (OPB) and oligopeptidase B2 (OPB2). These OPBs could be ideal targets, since both enzymes are expressed in all parasite lifecycle and were not identified in human. This work aimed to identify possible dual inhibitors of OPB and OPB2 from L. amazonensis. The threedimensional structures of both enzymes were built by comparative modelling and used to perform a virtual screening of ZINC database by DOCK Blaster server. It is the first time that OPB models from L. amazonensis are used to virtual screening approach. Four hundred compounds were identified as possible inhibitors to each enzyme. The top scored compounds were submitted to refinement by AutoDock program. The best results suggest that compounds interact with important residues, as Tyr490, Glu612 and Arg655 (OPB numbers). The identified compounds showed better results than antipain and drugs currently used against leishmaniasis when ADMET in silico were performed. These compounds could be explored in order to find dual inhibitors of OPB and OPB2 from L. amazonensis.
机译：Leishmaniaisis是Leishmania属的寄生虫引起的疾病，并通过亚家族痰麦芽肿的感染昆虫传播给人类。目前的药物疗法显示出高毒性和严重的不良反应。最近，在Leishmania Amazonensis中鉴定了两种寡肽（OPB），即寡肽酶B（OPB）和寡肽酶B2（OPB2）。这些OPB可以是理想的靶标，因为两种酶在所有寄生虫生命周期中都表达，并且未在人体中鉴定。这项工作旨在识别来自L.Amazonensis的可能的OPB和OPB2的可能的双重抑制剂。两种酶的三维结构由比较建模构建，并用于通过Dock Blaster服务器执行Zinc数据库的虚拟筛选。这是第一次来自L.Amazonensis的OPB模型用于虚拟筛选方法。将四百种化合物鉴定为每种酶可能的抑制剂。通过Autodock计划提交了较高的复制化合物。最佳结果表明，化合物与重要的残留物相互作用，如TYR490，GLU612和ARG655（OPB号）。鉴定的化合物表现出比目前在硅藻中的射击射击时使用的反引象和药物的效果更好。可以探索这些化合物，以便从L.Amazonensis找到OPB和OPB2的双重抑制剂。

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