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. 2019 Aug 22;9(45):26429-26434.
doi: 10.1039/c9ra03485d. eCollection 2019 Aug 19.

Increase in the apparent intercalation ability of a platinum complex via multivalency by installation into the sidechain of a graft copolymer and observation of structural changes in the intercalated DNA

Shigehito Osawa  1   2 , Riichi Takahashi  2 , Remi Watanabe  2 , Sayaka Kubo  2 , Hidenori Otsuka  1   2   3
Affiliations

Increase in the apparent intercalation ability of a platinum complex via multivalency by installation into the sidechain of a graft copolymer and observation of structural changes in the intercalated DNA

Shigehito Osawa et al. RSC Adv. .

Abstract

Metal complexes with planar structures have been utilized as DNA intercalators that can be inserted into the base pairs of DNA strands, and have potential applications in DNA-targeting drug therapies. When designing the intercalator metal complexes, controlling their interactions with DNA is important, and has been performed by modifying the chemical structure of the metal ligand. Herein, we designed a graft copolymer segment having Pt complexes with bipyridine and poly(ethylene glycol) (p(PEGMA-co-BPyMA-Pt)) as another strategy to control the interaction with DNA via a multivalent effect. The p(PEGMA-co-BPyMA-Pt) increased not only the binding constant as one macromolecule but also the apparent binding constant per intercalator unit compared to the Pt complex with bipyridine (BPy-Pt). Moreover, p(PEGMA-co-BPyMA-Pt) induced a larger change in DNA structure using lower amounts of Pt than BPy-Pt. These observed properties of p(PEGMA-co-BPyMA-Pt) suggest that grafting intercalators on polymer segments is a promising approach for designing novel types of intercalators.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Schematic illustration of polymerized platinum complex and its multivalent effect.
Fig. 1
Fig. 1. EtBr exclusion assays. Tracking fluorescence intensity change of (a) 4 μM EtBr solution containing 0.0117 mg mL−1 of CT-DNA with escalating addition of BPy (▲), p(PEGMA-co-BPyMA) (▼), BPy-Pt (■), and p(PEGMA-co-BPyMA-Pt) (●), (b) 2 μM EtBr solution containing 0.00585 mg mL−1 of CT-DNA with escalating addition amount of BPy-Pt, (c) 4 μM EtBr solution containing 0.0117 mg mL−1 of CT-DNA with escalating addition of Pt complex with series of p(PEGMA-co-ByMA-Pt/ByMA) at BPyMA-Pt/BPyMA ratio of 23/77, 50/50, 67/33 and 100/0, and (d) 4 μM EtBr solution containing 0.0117 mg mL−1 of CT-DNA with escalating addition of p(PEGMA-co-BPyMA-Pt/BPyMA) at BPyMA-Pt/BPyMA ratio of 50/50 (○) and 100/0 (●).
Fig. 2
Fig. 2. CD spectra of CT-DNA incubated with (a) BPy-Pt and (b) p(PEGMA-co-BPyMA-Pt) at various Pt/P ratios.
Fig. 3
Fig. 3. Gel images of pDNA incubated with escalating concentration of (a) BPy-Pt and (b) p(PEGMA-co-BPyMA-Pt).
Fig. 4
Fig. 4. Representative micrographs of pDNA incubated with BPy-Pt at feeding ratio of Pt/P = (a) 0.07, (c) 0.17 and (e) 0.23, and incubated with p(PEGMA-co-BPyMA-Pt) at feeding ratio of Pt/P = (b) 0.07, (d) 0.17 and (f) 0.23.
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