HBx衍生的受约束肽抑制乙型肝炎病毒抗原的分泌。

StephenW

Mol Pharm. 2018 Oct 30. doi: 10.1021/acs.molpharmaceut.8b00807. [Epub ahead of print]
HBx-derived constrained peptides inhibit the secretion of hepatitis B virus antigens.
Cai X, Zheng W, Shi X, Chen L, Liu Z, Li Z.
Abstract

Hepatitis B virus (HBV) infection is the primary cause of cirrhosis and liver cancer. Protein-protein interactions (PPIs) between HBV x protein (HBx) and its host targets including Bcl-2 are important for cell death and viral replication. No modulators targeting these PPIs have been reported yet. Here, we developed HBx-derived constrained peptides generated by a facile macrocyclization method by joining two methionine side chains of unprotected peptides with chemoselective alkylating linkers. The resulting constrained peptides with improved cell permeability and binding affinity were effective anti-HBV modulators by blocking secretion of viral antigens. This study clearly demonstrated HBx as a potentially important PPI target and the potential application of this efficient peptide macrocyclization strategy for targeting key PPIs.

PMID:
    30375875
DOI:
    10.1021/acs.molpharmaceut.8b00807

StephenW

Mol Pharm。 2018年10月30日doi：10.1021 / acs.molpharmaceut.8b00807。 [提前打印]
HBx衍生的受约束肽抑制乙型肝炎病毒抗原的分泌。
蔡,,郑伟，施昕，陈璐，刘,,李..
抽象

乙型肝炎病毒（HBV）感染是肝硬化和肝癌的主要原因。 HBV x蛋白（HBx）与其宿主靶标（包括Bcl-2）之间的蛋白质 - 蛋白质相互作用（PPI）对于细胞死亡和病毒复制是重要的。尚未报道针对这些PPI的调节剂。在这里，我们通过将未保护肽的两个甲硫氨酸侧链与化学选择性烷化接头连接，开发了由易于大环化方法产生的HBx衍生的约束肽。通过阻断病毒抗原的分泌，所得的具有改善的细胞渗透性和结合亲和力的受约束肽是有效的抗HBV调节剂。该研究清楚地证明HBx是一种潜在的重要PPI靶标，并且这种有效的肽大环化策略可能用于靶向关键PPI。

结论：
    30375875
DOI：
    10.1021 / acs.molpharmaceut.8b00807
Mol Pharm. 2018 Nián 10 yuè 30 rì doi:10.1021/ Acs.Molpharmaceut.8B00807. [Tíqián dǎyìn]
HBx yǎnshēng de shòu yuēshù tài yìzhì yǐ xíng gānyán bìngdú kàngyuán de fēnmì.
Cài,, zhèng wěi, shī xīn, chén lù, liú,, lǐ..
Chōuxiàng

yǐ xíng gānyán bìngdú (HBV) gǎnrǎn shì gān yìnghuà hé gān'ái de zhǔyào yuányīn. HBV x dànbái (HBx) yǔqí sùzhǔ bǎbiāo (bāokuò Bcl-2) zhī jiān de dànbáizhí - dànbáizhí xiānghù zuòyòng (PPI) duìyú xìbāo sǐwáng hé bìngdú fùzhì shì zhòngyào de. Shàngwèi bàodào zhēnduì zhèxiē PPI de tiáojié jì. Zài zhèlǐ, wǒmen tōngguò jiāng wèi bǎohù tài de liǎng gè jiǎ liú ān suān cè liàn yǔ huàxué xuǎnzé xìng wán huà jiētóu liánjiē, kāifāle yóu yìyú dà huán huà fāngfǎ chǎnshēng de HBx yǎnshēng de yuēshù tài. Tōngguò zǔ duàn bìngdú kàngyuán de fēnmì, suǒdé de jùyǒu gǎishàn de xìbāo shèntòu xìng hé jiéhé qīnhélì de shòu yuēshù tài shì yǒuxiào de kàng HBV tiáojié jì. Gāi yánjiū qīngchǔ dì zhèngmíng HBx shì yī zhǒng qiánzài de zhòngyào PPI bǎbiāo, bìngqiě zhè zhǒng yǒuxiào de tài dà huán huà cèlüè kěnéng yòng yú bǎ xiàng guānjiàn PPI.

Jiélùn:
    30375875
DOI:
    10.1021/ Acs.Molpharmaceut.8B00807