Aminoglycoside antibiotics aggregate to form starch-like fibers on negatively charged surfaces and on phage λ-DNA
Aminoglycoside antibiotics aggregate to form starch-like fibers on negatively charged surfaces and on phage λ-DNA
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DOI：
10.1021/la049207m
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发表时间：
2004-10-12
期刊：
影响因子：
3.9
通讯作者：
Fuhrhop, JH
中科院分区：
文献类型：
--
作者：
Kopaczynska, M;Lauer, M;Fuhrhop, JH
水溶性抗生素妥布霉素、卡那霉素和新霉素自发地在带负电荷的表面（云母、石墨、DNA）上产生刚性纤维。原子力显微镜显示，在pH为7的云母上，妥布霉素的单链长度为几百纳米，直径为0.5 nm，双螺旋直径为1.0 nm，螺距为7 nm。在pH为13 (NaOH) ~ 15的条件下，云母表面的硅酸钠通道形成了均匀高度为2.4 nm、表观螺旋距为30 nm的长而坚硬的纤维。卡那霉素和新霉素的表现相似。从pH为7的非晶亲水性碳水溶液中获得了长度和宽度相似但没有二级结构的纤维，并用透射电镜对其进行了表征。在pH为7时，在云母上高度为1.0 nm的超长噬菌体lambda-DNA链与妥布霉素线圈不发生相互作用。然而，经EDTA处理后，妥布霉素处理后，无镁lambda-DNA链的高度从1.0 nm增加到3.8 nm，这表明被超分子纤维包裹。这些纤维可能与生物细胞中的f -肌动蛋白纤维相互作用，这将解释氨基糖苷对细菌细胞膜的侵袭性及其耳毒性。
The water-soluble (> 200 mg/mL) antibiotics tobramycin, kanamycin, and neomycin spontaneously produce rigid fibers on negatively charged surfaces (mica, graphite, DNA). Atomic force microscopy showed single strands of tobramycin on mica at pH 7 with a length of several hundred nanometers and a diameter of 0.5 nm and double helices with a diameter of 1.0 nm and a helical pitch of 7 nm. At pH 13 (NaOH) up to 15,mum long, rigid fibers with a uniform height of 2.4 nm and an apparent helical pitch of 30 nm were formed along the sodium silicate channels on the surface of mica. Kanamycin and neomycin behaved similarly. Fibers of similar length and width, but without secondary structure, were obtained from aqueous solutions at pH 7 on amorphous, hydrophilized carbon and characterized by transmission electron microscopy. Overstretched phage lambda-DNA strands with a height of 1.0 nm on mica did not interact with tobramycin coils at pH 7. After treatment with EDTA, however, the height of the magnesium-free lambda-DNA strands grew from 1.0 to 3.8 nm after treatment with tobramycin, which suggests a wrapping by the supramolecular fibers. Such fibers may interact with F-actin fibers in biological cells, which would explain the known aggressiveness of aminoglycosides toward bacterial cell membranes and their ototoxicity.