RRC ID |
64572
|
Author |
Rana U, Chakraborty C, Pandey RK, Hossain MD, Nagano R, Morita H, Hattori S, Minowa T, Higuchi M.
|
Title |
Selective DNA Recognition and Cytotoxicity of Water-Soluble Helical Metallosupramolecular Polymers.
|
Journal |
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.
|
Volume |
27(10)
|
Pages |
2307-2314
|
Published |
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
|
Resource |
Human and Animal Cells |
A549(RCB0098) |