Per(6-guanidino-6-deoxy)cyclodextrins: synthesis, characterisation and binding behaviour toward selected small molecules and DNA
Per(6-guanidino-6-deoxy)cyclodextrins: synthesis, characterisation and binding behaviour toward selected small molecules and DNA
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DOI：
10.1039/b614899a
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发表时间：
2007-01-01
影响因子：
3.2
通讯作者：
Yannakopoulou, Konstantina
中科院分区：
文献类型：
--
作者：
Mourtzis, Nikolaos;Eliadou, Kyriaki;Yannakopoulou, Konstantina
全（6-胍基-6-脱氧）-环糊精4a、4 b和4c是新的衍生物，由在α-、β-和γ-环糊精的初级侧均匀引入胍基而产生。产物由相应的氨基衍生物获得，因为已知的溴-环糊精的直接胍基化提供了混合物。新化合物通过核磁共振光谱和其他分析方法进行了充分的表征，并研究了它们与客体分子的相互作用。观察到与4-硝基苯磷酸（NPP）二钠盐的强络合（K-结合类似于5 × 10（4）M-1），而非磷酸化底物硝基苯（NB）形成非常弱的络合物。2D ROESY光谱显示在两种情况下都有空腔夹杂物，然而NPP的取向与NB的取向相反，使得磷酸基团朝向面向胍基团的初级侧取向。4对磷酸化客体的强亲和力表明与DNA的相互作用是可能的。发现新化合物在琼脂糖凝胶电泳过程中完全抑制超纯小牛胸腺DNA的迁移，而单独使用胍或使用普通环糊精均未观察到影响。此外，通过原子力显微镜证实了在4 b存在下DNA缩合成纳米颗粒，证实了生物聚合物和多阳离子产物4之间的强静电相互作用。因此，4和DNA之间的强胍-磷酸相互作用归因于胍基团在环糊精的主要区域中的聚集。无法评估空洞效应。
Per(6-guanidino-6-deoxy)-cyclodextrins 4a, 4b and 4c are novel derivatives, resulting from homogeneous introduction of the guanidino group at the primary side of alpha-, beta- and gamma-cyclodextrins. The products were obtained from the corresponding amino derivatives, as direct guanidinylation of the known bromo-cyclodextrins provided mixtures. The new compounds were fully characterized by NMR spectroscopy and other analytical methods, and their interaction with guest molecules was studied. Strong complexation with 4-nitrophenyl phosphate (NPP) disodium salt was observed (K-binding similar to 5 x 10(4) M-1), whereas the non-phosphorylated substrate nitrobenzene (NB) formed a very weak complex. 2D ROESY spectra revealed cavity inclusion in both cases, however the orientation of NPP was opposite to that of NB, such that the phosphate group is oriented toward the primary side facing the guanidine groups. The strong affinity of 4 towards the phosphorylated guest suggested that interaction with DNA was possible. The new compounds were found to completely inhibit the migration of ultra pure calf thymus DNA during agarose gel electrophoresis, whereas no effects were observed with guanidine alone or with the plain cyclodextrins. Further, the condensation of DNA into nanoparticles in the presence of 4b was demonstrated by atomic force microscopy, confirming strong electrostatic interaction between the biopolymer and the multicationic products 4. The strong guanidine - phosphate interactions between 4 and DNA were therefore attributed to the clustering of the guanidine groups in the primary area of the cyclodextrin. Cavity effects could not be assessed.