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.

人乳头瘤病毒（HPV）是子宫颈癌的主要原因，只有某些HPV类型的疫苗可以预防，而病毒感染本身则无法治疗。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-天冬氨酸和谷氨酸官能化的杯[4]芳烃和亚氨基二乙酸官能化的杯[4]芳烃，并测试了其对L1五聚体形成的抑制作用。氨基酸官能化的杯[4]芳烃衍生物具有毫摩尔抑制作用（IC ₅₀ = 0.72至2.67 mM）的五聚体形成，立体异构体之间几乎没有差异。亚氨基二乙酸杯[4]芳烃衍生物没有抑制性，尽管与其他四个杯[4]芳烃具有相似的结构。通过胰蛋白酶消化来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可预防HPV组装的经济有效的抑制剂。