Interaction of oligodeoxynucleotides with mycobacteria: implications for new therapeutic strategies.
Interaction of oligodeoxynucleotides with mycobacteria: implications for new therapeutic strategies.
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寡脱氧核苷酸与分枝杆菌的相互作用：对新治疗策略的影响。
DOI：
10.1089/oli.1.1998.8.207
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Hughes,JA
中科院分区：
文献类型：
--
作者：
Attia,SA;Shepherd,VE;Rosenblatt,MN;Davidson,MK;Hughes,JA
使用合成的寡核苷酸(ONS)系统地解决分枝杆菌的新药理靶点，将促进引入新的药物干预分子靶点。寡核苷酸的作用机制允许研究人员在不需要纯化样本的情况下研究特定蛋白质的重要性。为了使这种方法有效，分枝杆菌必须能够将ONS运输到它们的细胞质，如果不是这样，就必须以其他方式递送试剂。在这份报告中，我们表征了硫代磷酸酯(PS)和磷酸二酯(PD)ONS与耻垢分枝杆菌和结核分枝杆菌的相互作用能力。此外，我们还评估了递送促进剂乙胺丁醇和PAMAM树状大分子对分枝杆菌相互作用的影响。On的相互作用是浓度依赖的，这可能是寡核苷酸和细菌相互作用的活性成分。通过细菌与给药佐剂的共孵育，可以增加On的相互作用。乙胺丁醇或树枝状大分子(第四代)的治疗被证明增加了与这两种分枝杆菌的相互作用，尽管程度不同。这些初步实验的结果表明，通过使用适当的给药佐剂，可以增加与分枝杆菌的相互作用。这些发现可能对探索未来的抗分枝杆菌治疗靶点有一定的意义。
The use of synthetic oligonucleotides (ONs) to systematically address new pharmacologic targets in mycobacteria would enhance the introduction of new molecular targets for drug intervention. Oligonucleotides' mechanism of action allows researchers to pursue the importance of particular proteins without the requirement of having purified samples. For this approach to be effective, mycobacteria must be able to transport ONs to their cytoplasm, and if this is not the case, the agents must be otherwise delivered. In this report, we characterize the ability of phosphorothioate (PS) and phosphorodiester (PD) ONs to interact with bothMycobacterium smegmatis and Mycobacterium tuberculosis.In addition, the use of delivery enhancer compounds, ethambutol and PAMAM dendrimer, was evaluated on the ON-mycobacteria interaction. ON interaction was demonstrated to be concentration-dependent, suggesting a possibly active component of the oligonucleotide and bacteria interaction. ON interaction could be increased by the coincubation of the bacteria with the delivery adjuvants. Treatment with ethambutol or dendrimers (fourth generation) was demonstrated to increase ON interaction with both species of mycobacteria although not to the same extent. The results of these preliminary experiments indicate that through use of the proper delivery adjuvant, ON interactions with mycobacteria can be increased. These findings may have implications for probing future antimycobacterial therapeutic targets.