区域选择性硫化玻尿酸衍生物与对1型简单疹病毒的活性之间的结构关系
Gabrielle Cristina Calegari1, Mario Gabriel Lopes Barboza2, André Luiz Dyna2
1Departamento de Química, CCE, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
International journal of biological macromolecules
|June 20, 2024
概括
硫酸的真菌β-葡萄糖显示出抗病毒性质. 玻尿衍生物在C-6位置的硫化显著抑制了简单疹病毒1型 (HSV-1) 通过阻断病毒吸附.
科学领域:
- 生物化学 生物化学
- 病毒学 病毒学
- 碳水化合物化学 碳水化合物化学
背景情况:
- 硫酸多糖的生物活性通常与它们的特定替代模式有关.
- 菌多糖类,如玻尿酸,正在探索治疗潜力.
- 了解结构-活性关系对于开发新型抗病毒药物至关重要.
研究的目的:
- 为了研究硫化模式对玻尿衍生物抗病毒活性的影响.
- 通过轻微硫化 (MS) 和pivaloyl ester (PS) 方法合成和表征区域选择性硫化玻尿酸.
- 评估这些衍生品对简单疹病毒1型 (HSV-1) 和登革热2型 (DENV-2) 的抗病毒疗效.
主要方法:
- 通过两种不同的化学方法对真菌 (1→3) ((1→6) -β-D-glucan (botryosphaeran) 进行区域选择性硫化:轻度硫化 (MS) 和pivaloyl ester (PS) 合成.
- 由此产生的硫衍生物的化学表征,以确定替代度和模式.
- 针对HSV-1 (KOS菌株) 和DENV-2的体外抗病毒测定,包括IC50值的确定.
- 活性衍生物的作用机制研究,重点关注病毒吸附抑制.
主要成果:
- 获得了两种硫化玻尿酸衍生物,其替代度为0.82 (MS) 和0.49 (PS).
- 在C-6位置替换的MS衍生物对HSV-1具有显著的抗病毒活性,IC50为5.38μg/mL.
- 在C-2/C-4位置替换的PS衍生品,没有显示针对HSV-1或DENV-2的抗病毒活性.
- 发现活性MS衍生物抑制HSV-1吸附到宿主细胞.
结论:
- 硫酸多糖的替代模式决定了它们的生物活性.
- 玻里奥斯法兰在C-6位置的硫化对于对HSV-1的强有力的抗病毒活性至关重要.
- 玻尿衍生物显示出作为抗病毒剂的前景,C-6硫化是HSV-1抑制的关键结构特征.
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