Selection of HBV preS1-binding penta-peptides by phage display
Selection of HBV preS1-binding penta-peptides by phage display
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通过噬菌体展示选择 HBV preS1 结合五肽
DOI：
10.1093/abbs/gmu049
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发表时间：
2014-08-01
影响因子：
3.7
通讯作者：
Xie, Youhua
中科院分区：
文献类型：
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作者：
He, Yonggang;Ye, Xiaoli;Xie, Youhua
慢性乙型肝炎病毒（HBV）感染可导致肝硬化和肝细胞癌。目前的疗法在清除病毒方面的功效非常有限。迫切需要新的抗病毒靶点和药物。 HBV病毒颗粒的包膜含有三种表面糖蛋白，即大蛋白（LHBs）、中蛋白（MHBs）和小蛋白（SHBs）。 LHBs 具有氨基末端 preS，由 preS1 和 preS2 结构域组成。 preS1 的氨基一半被肉豆蔻酰化，在 HBV 进入中发挥着关键作用，可用作抗病毒靶点。先前已发现五个氨基酸的共同基序可结合 preS1(1-65) 和 HBV 颗粒。在本研究中，我们使用preS1(1-65)筛选随机五肽的噬菌体展示文库，以选择具有高preS1结合亲和力的五肽。经过九轮淘选，我们获得了一种肽，命名为A5，它可以以高亲和力结合preS1。通过系统地用其他 19 个氨基酸取代 A5 的每个残基，我们鉴定了一种具有增加的 preS1 结合亲和力的新肽。这两种肽都可以抑制 HBV 附着于 HepG2 细胞，使其成为 HBV 进入抑制剂的潜在候选者。
Chronic hepatitis B virus (HBV) infection can lead to liver cirrhosis and hepatocellular carcinoma. Current therapies have a very limited efficacy in virus clearance. New antiviral targets and agents are urgently needed. The envelope of HBV virion contains three surface glycoproteins, namely the large (LHBs), middle (MHBs), and small (SHBs) proteins. LHBs has an amino terminal preS which is composed of the preS1 and preS2 domains. The amino half of preS1 which is myristoylated plays a pivotal role in HBV entry, which can be exploited as an antiviral target. A common motif of five amino acids had been previously discovered to bind preS1(1-65) and HBV particles. In this study, we used preS1(1-65) to screen a phage display library of random penta-peptides to select the penta-peptides possessing a high preS1-binding affinity. After nine rounds of panning, we obtained one peptide designated as A5 which could bind preS1 with a high affinity. By systematically substituting each residue of A5 with the other 19 amino acids, we identified a novel peptide with an increased preS1-binding affinity. Both peptides could inhibit HBV attachment to HepG2 cells, making them be potential candidates for HBV entry inhibitors.