人乳头瘤病毒(HPV)衣壳蛋白多级组装的多金属氧簇(POMs)调控及组装体性能研究

Infection of high risk human papillomavirus (HPVs) causes various malignant tumors, it is urgent need to develop the new generation of anti-HPV agents. The linear epitopes in the minor capsid protein L2 are the highly conserved and succession extended amino acids which can be graft on other backbone easily but keep their immunity well, and therefore, it has become a new focus to develop a broad-spectrum anti-HPV agents. The potential bio-applications of polyoxometalates (POMs) push us to introduce them to monitor the assemblies of HPV L1 protein and L2 peptides (L2pep), to create highly stable, broad-spectrum anti-HPV new materials. For that, multi-scaled assemblies will be performed between (1) L2pep and POMs to create L2pep-POMs; (2) L2pep-POMs and L1 pentamer (L1-p) to generate L2pep-POMs@VLP; (3) VLPs and/or L2pep-POMs@VLP to stabilize the final products before use. Both the driving forces and key factors to regulate the multi-scaled assemblies will be focused to reveal the intrinsic mechanism and involved kinetic at molecular level. The functions of the newly created materials, particularly the newly developed and synergistic enhancement ones from assembly will be paid special attention in performance. The present study will provide new theoretical basis and technical supports for the research and development of anti-HPV drugs in future.

高危型人乳头瘤病毒(HPVs)是多种恶性肿瘤的直接诱因，发展新一代抗HPV制剂迫在眉睫。HPV次要衣壳蛋白L2的抗原是由序列连续且高度保守的氨基酸组成的“线性表位”，可以直接被嫁接到其它载体上而发挥功能，是研发新一代抗HPV制剂的焦点。基于多金属氧簇(POMs)的潜在生物学应用，我们拟将它们引入到HPV衣壳蛋白L1或L2抗原表位肽(L2pep)的多重组装调控中, 拟在三个不同层次开展杂合组装调控：(1) L2pep与POMs; (2) L2pep-POMs组装体与L1五聚体; (3) 以类病毒粒子(VLPs)及其杂合组装体为构筑基元的更高级别组装。开发稳定性好、免疫性高且广谱的新型生物-无机抗病毒材料。重点研究多级组装中的主要驱动力及关键调控因素，揭示内在分子机理和机制；考察由组装带来的原有各组装基元生物学性能的协同增强性和材料新功能，为抗HPVs药物的研发提供新的理论依据和技术支持。

高危型人乳头瘤病毒(HPVs)是多种恶性肿瘤的直接诱因，发展新一代抗HPV制剂迫在眉睫。此外，多金属氧酸盐(POMs)以其优异的性能已在材料科学、生命科学以及医药等领域展示出很好的应用前景；然而，其较强的表面极性和较低的生物相容性有待进一步改进。基于人乳头瘤病毒(HPVs)的高入侵性和在HPV衣壳蛋白组装调控领域的研究基础，我们将含有钼或铕的POMs引入到人乳头瘤病毒(HPVs)衣壳蛋白或其相关肽的研究中，分别在三个不同层次：（1）HPV相关肽与POMs；（2）HPV L1五聚体与POMs：（3）HPV类病毒粒子(VLPs)与POMs开展了多重组装调控研究，得到了多系列不同级别的生物-无机杂合功能材料。并系统研究了它们在细胞内荧光成像、抗菌消炎、抗肿瘤、以及抗病毒等领域中的应用，重点考察了由组装带来的协同增强性能和材料生物学新功能；并深入揭示了其发挥功能的内在分子机理和作用机制，为抗HPVs药物的研发和拓展POMs的生物学应用提供了新的理论依据和技术支持。