RRC ID 64572
著者 Rana U, Chakraborty C, Pandey RK, Hossain MD, Nagano R, Morita H, Hattori S, Minowa T, Higuchi M.
タイトル Selective DNA Recognition and Cytotoxicity of Water-Soluble Helical Metallosupramolecular Polymers.
ジャーナル Bioconjug Chem
Abstract 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 (Kb = 13.08 × 107 M-1) to ct-DNA than (M)-polyFe. The differences in binding affinity were supported by electrochemical impedance spectroscopy analysis. The charge-transfer resistance (Rct) 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.
巻・号 27(10)
ページ 2307-2314
公開日 2016-10-19
DOI 10.1021/acs.bioconjchem.6b00255
PMID 27580353
MeSH Animals Antineoplastic Agents / chemistry Antineoplastic Agents / metabolism Antineoplastic Agents / pharmacology* Apoptosis / drug effects Chemistry Techniques, Synthetic DNA / metabolism* Dielectric Spectroscopy / methods Drug Screening Assays, Antitumor / methods Fluoresceins / metabolism Humans Iron Compounds / chemistry Mice Microscopy, Atomic Force NIH 3T3 Cells / drug effects Polymers / chemistry* Polymers / metabolism* Polymers / pharmacology Solubility Water / chemistry
IF 4.031
リソース情報
ヒト・動物細胞 A549(RCB0098)