Epstein–Barr virus (EBV) establishes latent infection and is associated with several types of lymphomas and carcinomas. EBV nuclear antigen 1 (EBNA1) is expressed in all EBV-positive tumor cells. EBNA1 binds to the origin of virus plasmid replication (OriP) on the EBV episome to initiate virus DNA replication and regulates virus gene expression as a transcriptional activator. In this study, we designed and synthesized a pyrrole–imidazole polyamide–Hoechst 33258 conjugate named EIP-2 (2), which specifically binds to the OriP region with high affinity, to interrupt EBNA1-OriP binding in vitro and in vivo. By eradicating the EBV episome in EBV-positive cells, compound 2 selectively inhibited EBV-positive cell proliferation. Moreover, the injection of 2 significantly suppressed tumor growth in the mice xenograft tumor model. These findings demonstrate that compound 2 is a potential therapeutic candidate for the treatment of EBV-associated tumors.

中文翻译：

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新型吡咯-咪唑聚酰胺Hoechst偶联物可抑制爱泼斯坦-巴尔病毒复制和病毒阳性肿瘤的生长

爱泼斯坦巴尔病毒（EBV）建立潜在的感染，并与几种类型的淋巴瘤和癌相关。EBV核抗原1（EBNA1）在所有EBV阳性肿瘤细胞中表达。EBNA1与EBV附加体上病毒质粒复制（OriP）的起点结合，以启动病毒DNA复制并调节病毒基因的表达作为转录激活因子。在这项研究中，我们设计并合成了名为EIP-2（2）的吡咯-咪唑聚酰胺-Hoechst 33258共轭物，该共轭物以高亲和力特异性结合OriP区，以在体外和体内中断EBNA1-OriP结合。通过消除EBV阳性细胞中的EBV附加体，化合物2选择性抑制EBV阳性细胞增殖。而且，注射2显着抑制了小鼠异种移植肿瘤模型中的肿瘤生长。这些发现表明，化合物2是用于治疗与EBV相关的肿瘤的潜在治疗候选物。