Zsila Ferenc
Research Group of Chemical Biology, Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, POB 289, H-1519, Budapest, Hungary.
Phys Chem Chem Phys. 2015 Oct 14;17(38):24560-5. doi: 10.1039/c5cp03153b.
It is shown that the antiprotozoal drugs berenil and pentamidine, conventional minor groove binders of DNA, form non-covalent complexes with polyanionic glycosaminoglycans. Induced circular dichroism (CD) spectra as well as UV hypochromism confirmed drug binding to the asymmetric template of heparin and chondroitin 6-sulfate. The biphasic nature of the CD signals refers to intermolecular chiral exciton coupling between the dicationic guest molecules forming a right- or a left-handed helical array along the GAG chains. Quantitative evaluation of the spectroscopic data measured in pH 7.0 buffer solution (80 mM NaCl) indicated a higher (Ka ∼ 10(6) M(-1) for berenil) and a lower (Ka ∼ 10(5) M(-1) for pentamidine) affinity heparin binding of these agents, similar to that reported for DNA. Drug-chondroitin sulfate complexes (Ka ∼ 10(4)-10(5) M(-1)) could be detected only at low ionic strength. These results imply that besides nucleic acids, GAGs may be another pharmacological targets for diarylamidine drugs.
结果表明，抗原虫药物贝尼尔和喷他脒作为传统的DNA小沟结合剂，可与聚阴离子糖胺聚糖形成非共价复合物。诱导圆二色性（CD）光谱以及紫外减色效应证实了药物与肝素和硫酸软骨素6 - 硫酸酯的不对称模板结合。CD信号的双相性质是指沿着糖胺聚糖链形成右手或左手螺旋阵列的双阳离子客体分子之间的分子间手性激子耦合。在pH 7.0缓冲溶液（80 mM NaCl）中测量的光谱数据的定量评估表明，这些药物与肝素结合的亲和力较高（贝尼尔的Ka ∼ 10(6) M(-1)）和较低（喷他脒的Ka ∼ 10(5) M(-1)），与报道的与DNA结合的情况类似。药物 - 硫酸软骨素复合物（Ka ∼ 10(4)-10(5) M(-1)）仅在低离子强度下才能检测到。这些结果表明，除了核酸外，糖胺聚糖可能是二脒基药物的另一个药理学靶点。
