新型含氟胞苷肽化合物SN15的大规模合成和抗病毒机制:来自转录组学和蛋白质组学分析的见解

IF 4 1区 农林科学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Miao Yu , Chuantao Xu , Yan Wang , Shidong Zhou , Jingwen Li , Zihao Xia , Mengnan An , He Liu , Yuanhua Wu
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引用次数: 0

摘要

胞苷肽化合物已成为抗病毒药物的有希望的候选药物,但其大规模生产和作用方式仍未得到充分探索。通过优化温度控制和搅拌效率,以HCl/二氧六环体系代替三氟乙酸进行叔丁基氧羰基(Boc)脱保护,无需柱层析纯化,高效制备了SN15,产率为78.47%。抗病毒实验显示,在250 μg/mL浓度下,SN15可抑制TMV在单细胞中的积累,抑制率为53.44%,并显著抑制PVY、PMMoV和TuMV的全身感染,使病毒RNA积累分别减少54.16%、41.14%和61.85%。转录组学分析发现9676个差异表达基因(deg),核糖体蛋白相关通路显著上调,激素信号/泛素化通路下调。蛋白质组学分析显示216种差异表达蛋白(dep),包括核糖体成分和应激反应蛋白,与转录组学趋势一致。TRV-VIGS结果显示,沉默60S核糖体蛋白L6或脂质转移样蛋白VAS可显著增加TMV积累,证实其在抗病毒防御中的关键作用,而沉默过氧化物酶N1前体和E3泛素蛋白连接酶cip8样异构体X1可抑制病毒复制。本研究揭示了SN15通过多途径协同调控发挥抗病毒作用的分子机制,为氟化胞苷肽化合物SN15的工业化生产和广谱抗病毒应用提供理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Scale-up synthesis and antiviral mechanisms of novel fluorine-containing cytidine peptide compound SN15: Insights from transcriptomic and proteomic analyses

Scale-up synthesis and antiviral mechanisms of novel fluorine-containing cytidine peptide compound SN15: Insights from transcriptomic and proteomic analyses
Cytidine peptide compounds have emerged as promising candidates for antiviral agents, but their large-scale production and mode of action remain underexplored. By optimizing temperature control and stirring efficiency, and replacing trifluoroacetic acid with an HCl/dioxane system for tert-butyloxycarbonyl (Boc) deprotection, efficient preparation of SN15 was achieved with a 78.47 % yield without the need for column chromatographic purification. Antiviral assays showed that SN15 inhibited TMV accumulation in single cells by 53.44 % at 250 μg/mL and significantly suppressed systemic infections by PVY, PMMoV, and TuMV, reducing viral RNA accumulation by 54.16 %, 41.14 %, and 61.85 %, respectively. Transcriptomic analysis identified 9676 differentially expressed genes (DEGs), with ribosomal protein-related pathways significantly upregulated and hormone signaling/ubiquitination pathways downregulated. Proteomic analysis revealed 216 differentially expressed proteins (DEPs), including ribosomal components and stress-response proteins, consistent with transcriptomic trends. Results of TRV-VIGS showed that silencing of 60S ribosomal protein L6 or lipid transfer-like protein VAS significantly increased TMV accumulation, confirming its critical role in antiviral defense, while silencing of peroxidase N1 precursor and E3 ubiquitin-protein ligase CIP8-like isoform X1 inhibited viral replication. This study reveals the molecular mechanism by which SN15 exerts antiviral effects through multi-pathway synergistic regulation, and provides a theoretical basis for the industrial production and broad-spectrum antiviral application of the fluorinated cytidine peptide compound SN15.
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来源期刊
CiteScore
7.00
自引率
8.50%
发文量
238
审稿时长
4.2 months
期刊介绍: Pesticide Biochemistry and Physiology publishes original scientific articles pertaining to the mode of action of plant protection agents such as insecticides, fungicides, herbicides, and similar compounds, including nonlethal pest control agents, biosynthesis of pheromones, hormones, and plant resistance agents. Manuscripts may include a biochemical, physiological, or molecular study for an understanding of comparative toxicology or selective toxicity of both target and nontarget organisms. Particular interest will be given to studies on the molecular biology of pest control, toxicology, and pesticide resistance. Research Areas Emphasized Include the Biochemistry and Physiology of: • Comparative toxicity • Mode of action • Pathophysiology • Plant growth regulators • Resistance • Other effects of pesticides on both parasites and hosts.
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