Rana Utpal, Chakraborty Chanchal, Pandey Rakesh K, Hossain Md Delwar, Nagano Reiko, Morita Hiromi, Hattori Shinya, Minowa Takashi, Higuchi Masayoshi
Electronic Functional Macromolecules Group, National Institute for Materials Science (NIMS) , Tsukuba 305-0044, Japan.
International Center for Materials Nanoarchitectonics (MANA), NIMS , Tsukuba 305-0044, Japan.
Bioconjug Chem. 2016 Oct 19;27(10):2307-2314. doi: 10.1021/acs.bioconjchem.6b00255. Epub 2016 Sep 14.
Water-soluble helical Fe(II)-based metallosupramolecular polymers ((P)- and (M)-polyFe) were synthesized by 1:1 complexation of Fe(II) ions and bis(terpyridine)s bearing a (R)- and (S)-BINOL spacer, respectively. The binding affinity to calf thymus DNA (ct-DNA) was investigated by titration measurements. (P)-PolyFe with the same helicity as B-DNA showed 40-fold higher binding activity (K = 13.08 × 10 M) to ct-DNA than (M)-polyFe. The differences in binding affinity were supported by electrochemical impedance spectroscopy analysis. The charge-transfer resistance (R) of (P)-polyFe increased from 2.5 to 3.9 kΩ upon DNA binding, while that of (M)-polyFe was nearly unchanged. These results indicate that ionically strong binding of (P)-polyFe to DNA chains decreased the mobility of ions in the conjugate. Unique rod-like images were obtained by atomic force microscopy measurement of the DNA conjugate with (P)-polyFe, likely because of the rigid binding between DNA chains and the polymer. Differences in polymer chirality lead to significantly different cytotoxicity levels in A549 cells. (P)-PolyFe showed higher binding affinity to B-DNA and much higher cytotoxicity than (M)-polyFe. The helicity in metallosupramolecular polymer chains was important not only for chiral recognition of DNA but also for coordination to a biological target in the cellular environment.
通过分别使亚铁离子与带有（R）-和（S）-联萘酚间隔基的双（三联吡啶）以1:1络合，合成了水溶性螺旋状亚铁基金属超分子聚合物（（P）-聚铁和（M）-聚铁）。通过滴定测量研究了其对小牛胸腺DNA（ct-DNA）的结合亲和力。与B-DNA具有相同螺旋度的（P）-聚铁对ct-DNA的结合活性（K = 13.08×10 M）比（M）-聚铁高40倍。电化学阻抗谱分析证实了结合亲和力的差异。（P）-聚铁与DNA结合后，其电荷转移电阻（R）从2.5 kΩ增加到3.9 kΩ，而（M）-聚铁的电荷转移电阻几乎不变。这些结果表明，（P）-聚铁与DNA链之间的强离子结合降低了共轭物中离子的迁移率。通过对与（P）-聚铁形成的DNA共轭物进行原子力显微镜测量，获得了独特的棒状图像，这可能是由于DNA链与聚合物之间的刚性结合所致。聚合物手性的差异导致A549细胞中细胞毒性水平有显著差异。（P）-聚铁对B-DNA的结合亲和力更高，细胞毒性也比（M）-聚铁高得多。金属超分子聚合物链中的螺旋度不仅对手性识别DNA很重要，而且对在细胞环境中与生物靶标的配位也很重要。
