ABSTRACT Human Papillomavirus (HPV) is the leading cause of cervical cancer, with only some HPV types prevented with vaccines and no treatments for the viral infection itself. One way to target viral infection is by inhibiting the assembly of the L1 monomer into a pentamer, which forms the viral capsid. Four calix[4]arene compounds functionalised with D- and L-aspartic and glutamic acid and an iminodiacetic functionalised calix[4]arene were synthesised and tested for L1 pentamer formation inhibition. The amino acid functionalised calix[4]arene derivatives showed millimolar inhibition (IC50 = 0.72 to 2.67 mM) of pentamer formation, with little difference between the stereoisomers. The iminodiacetic acid calix[4]arene derivative showed no inhibitory properties, despite sharing structural similarities with the four other calix[4]arenes. Confirmation of binding the negatively charged compounds to the positive residues of the L1 protein was achieved by trypsin digestion. This study is helpful in the development of cost-effective inhibitors to prevent HPV assembly. Graphical abstract

中文翻译：

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酸性官能化杯[4]芳烃对人乳头瘤病毒五聚体形成的抑制作用

摘要 人乳头瘤病毒 (HPV) 是宫颈癌的主要原因，只有部分 HPV 类型可以通过疫苗预防，并且没有针对病毒感染本身进行治疗。靶向病毒感染的一种方法是抑制 L1 单体组装成五聚体，从而形成病毒衣壳。合成了四种用 D-和 L-天冬氨酸和谷氨酸功能化的杯 [4] 芳烃化合物和一个亚氨基二乙酸官能化的杯 [4] 芳烃，并测试了 L1 五聚体形成的抑制作用。氨基酸官能化杯[4]芳烃衍生物显示出对五聚体形成的毫摩尔抑制（IC50 = 0.72 至 2.67 mM），立体异构体之间几乎没有差异。亚氨基二乙酸杯[4]芳烃衍生物尽管与其他四种杯[4]芳烃具有相似的结构，但没有显示出抑制特性。通过胰蛋白酶消化确认带负电荷的化合物与 L1 蛋白的正残基结合。这项研究有助于开发具有成本效益的抑制剂以防止 HPV 组装。图形概要