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选择聚烯基复合物修饰的适合剂,用于对抗Streptococcus肺炎的光动力疗法

Marie Flamme^1,2, Germain Niogret^1,2, Luke McKenzie^1,2

¹Institut Pasteur, Université Paris Cité, CNRS UMR3523, Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, 28, Rue du Docteur Roux, Paris 75724 Cedex 15, France.

Journal of the American Chemical Society

|November 8, 2025

概括

这项研究开发了使用复合体向细菌进行光动力学疗法 (PDT) 的新型受体. 这些阿巴美尔-药物合物显示出对抗抗微生物耐药性 (AMR) 的承诺,通过增强PDT对病原体的疗效,如Streptococcus pneumoniae.

科学领域:

生物化学生物化学
分子生物学分子生物学
抗菌研究抗菌研究

背景情况:

光动力学疗法 (PDT) 使用光,氧和光敏感剂来产生反应性氧物种 (ROS) 进行细胞死亡.
抗菌素耐药性 (AMR) 是一个日益增长的全球健康威胁,需要新的治疗策略.
当前的PDT方法在向细菌时面临着特异性和生物膜透方面的挑战.

研究的目的:

设计具有聚基复合物的功能化体,用于增强PDT对抗阳性细菌,特别是*Streptococcus pneumoniae*.
调查这些修改后的体的潜力,以提高光敏化特异性,PDT效率和生物膜透.
探索SELEX (指数式丰富联体的系统进化) 中修饰核酸的使用,以产生针对整个细菌细胞的体.

主要方法:

合成与鲁聚烯基复合体功能化的核酸,并评估它们的聚合酶基质能力.
进行SELEX以识别与*Streptococcus pneumoniae*结合的体.
描述未经修改和经修改的胺酸的结合亲和力 (K_d) 和二次结构 (UV化,T_m).

主要成果:

鲁复合体显示出强烈的双链DNA间隙,即使与负电荷的脊柱相连.
两种未经修改的体表现出对*Streptococcus pneumoniae*的高结合亲和力 (K_d=118 nM和541 nM).
鉴定了一种修饰的阿普坦体,其K_d值为125nM,尽管对二次结构形成存在挑战 (T_m=84°C).

结论:

携带大量修饰的核酸,如聚烯基复合物,可以在SELEX中有效地用于产生针对细菌点的强有力的aptamers.
这些发现支持开发基于aptamer的策略,通过增强光动力学疗法对抗AMR.
工程制造的aptamers显示出作为细菌感染的向治疗剂的潜力,特别是那些涉及生物膜的细菌感染.

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