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二氯化铂配合物与DNA分子间相互作用力的直接测量。

Direct measurement of interaction forces between a platinum dichloride complex and DNA molecules.

作者信息

Muramatsu Hiroshi, Shimada Shogo, Okada Tomoko

机构信息

School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo, 192-0982, Japan.

New Histo. Science Laboratory Co., Ltd, 2-979-2 Kurosawa, Ohme, Tokyo, 198-0005, Japan.

出版信息

J Biol Phys. 2017 Sep;43(3):355-365. doi: 10.1007/s10867-017-9456-5. Epub 2017 Jun 29.

Abstract

The interaction forces between a platinum dichloride complex and DNA molecules have been studied using atomic force microscopy (AFM). The platinum dichloride complex, di-dimethylsulfoxide-dichloroplatinum (II) (Pt(DMSO)Cl), was immobilized on an AFM probe by coordinating the platinum to two amino groups to form a complex similar to Pt(en)Cl, which is structurally similar to cisplatin. The retraction forces were measured between the platinum complex and DNA molecules immobilized on mica plates using force curve measurements. The histogram of the retraction force for λ-DNA showed several peaks; the unit retraction force was estimated to be 130 pN for a pulling rate of 60 nm/s. The retraction forces were also measured separately for four single-base DNA oligomers (adenine, guanine, thymine, and cytosine). Retraction forces were frequently observed in the force curves for the DNA oligomers of guanine and adenine. For the guanine DNA oligomer, the most frequent retraction force was slightly lower than but very similar to the retraction force for λ-DNA. A higher retraction force was obtained for the adenine DNA oligomer than for the guanine oligomer. This result is consistent with a higher retraction activation energy of adenine with the Pt complex being than that of guanine because the kinetic rate constant for retraction correlates to exp(FΔx - ΔE) where ΔE is an activation energy, F is an applied force, and Δx is a displacement of distance.

摘要

已使用原子力显微镜(AFM)研究了二氯化铂配合物与DNA分子之间的相互作用力。二氯化铂配合物,二甲基亚砜二氯铂(II)(Pt(DMSO)Cl),通过使铂与两个氨基配位固定在AFM探针上,形成类似于Pt(en)Cl的配合物,其结构与顺铂相似。使用力曲线测量法测量了铂配合物与固定在云母片上的DNA分子之间的回缩力。λ-DNA回缩力的直方图显示出几个峰值;对于60 nm/s的拉伸速率,单位回缩力估计为130 pN。还分别测量了四种单碱基DNA寡聚物(腺嘌呤、鸟嘌呤、胸腺嘧啶和胞嘧啶)的回缩力。在鸟嘌呤和腺嘌呤的DNA寡聚物的力曲线中经常观察到回缩力。对于鸟嘌呤DNA寡聚物,最频繁的回缩力略低于但非常类似于λ-DNA的回缩力。腺嘌呤DNA寡聚物的回缩力高于鸟嘌呤寡聚物。该结果与腺嘌呤与铂配合物的回缩活化能高于鸟嘌呤一致,因为回缩的动力学速率常数与exp(FΔx - ΔE)相关,其中ΔE是活化能,F是施加的力,Δx是距离的位移。

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