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通过将铂配合物多价体安装到接枝共聚物的侧链中来提高其表观嵌入能力,并观察嵌入DNA的结构变化。

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

作者信息

Osawa Shigehito, Takahashi Riichi, Watanabe Remi, Kubo Sayaka, Otsuka Hidenori

机构信息

Department of Applied Chemistry, Faculty of Science Division I, Tokyo University of Science 1-3 Kagurazaka, Shinjuku-ku Tokyo 162-8601 Japan

Graduate School of Science, Tokyo University of Science 1-3 Kagurazaka, Shinjuku-ku Tokyo 162-8601 Japan.

出版信息

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

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--BPyMA-Pt)) as another strategy to control the interaction with DNA a multivalent effect. The p(PEGMA--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--BPyMA-Pt) induced a larger change in DNA structure using lower amounts of Pt than BPy-Pt. These observed properties of p(PEGMA--BPyMA-Pt) suggest that grafting intercalators on polymer segments is a promising approach for designing novel types of intercalators.

摘要

具有平面结构的金属配合物已被用作可插入DNA链碱基对中的DNA嵌入剂,在靶向DNA的药物治疗中具有潜在应用。在设计嵌入剂金属配合物时,控制它们与DNA的相互作用很重要,并且已经通过修饰金属配体的化学结构来实现。在此,我们设计了一种具有联吡啶铂配合物和聚乙二醇的接枝共聚物片段(p(PEGMA--BPyMA-Pt)),作为控制与DNA相互作用的另一种策略——多价效应。与联吡啶铂配合物(BPy-Pt)相比,p(PEGMA--BPyMA-Pt)不仅作为一个大分子增加了结合常数,而且每个嵌入剂单元的表观结合常数也增加了。此外,p(PEGMA--BPyMA-Pt)使用比BPy-Pt更少的铂就能诱导DNA结构发生更大的变化。p(PEGMA--BPyMA-Pt)的这些观察到的性质表明,在聚合物片段上接枝嵌入剂是设计新型嵌入剂的一种有前途的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bbd/9070401/46b1118c3290/c9ra03485d-s1.jpg

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