抗癌藥物奧沙利鉑與DNA分子相互作用的研究
發(fā)布時(shí)間:2018-01-13 18:17
本文關(guān)鍵詞:抗癌藥物奧沙利鉑與DNA分子相互作用的研究 出處:《生物化學(xué)與生物物理進(jìn)展》2016年07期 論文類型:期刊論文
更多相關(guān)文章: 奧沙利鉑 DNA 高定向熱解石墨 原子力顯微鏡
【摘要】:奧沙利鉑被稱為第三代鉑類藥物,特別對(duì)胃腸道腫瘤具有較好的療效.目前大多數(shù)的研究表明奧沙利鉑的主要作用靶點(diǎn)是DNA分子,但它與DNA分子形成的關(guān)鍵結(jié)構(gòu)和作用機(jī)制仍處在探索階段.本研究運(yùn)用紫外可見吸收光譜和原子力顯微鏡觀察探索奧沙利鉑與DNA在活體外的相互作用過程,從而揭示奧沙利鉑產(chǎn)生抗癌作用的主要分子結(jié)構(gòu)基礎(chǔ).首先使用紫外光譜研究了較高濃度奧沙利鉑與DNA的作用過程.在此基礎(chǔ)上,進(jìn)一步采用原子力顯微鏡在高定向熱解石墨表面觀察了不同濃度奧沙利鉑與質(zhì)粒DNA在37℃條件下作用不同時(shí)間后的結(jié)構(gòu)形貌變化,分析了奧沙利鉑與DNA相互作用的過程.高分辨原子力顯微觀察結(jié)果表明奧沙利鉑與DNA作用后可導(dǎo)致質(zhì)粒DNA的結(jié)構(gòu)發(fā)生顯著的變化.隨著作用時(shí)間的增加,DNA分子逐漸由伸展的鏈狀變化為相互纏繞并帶有許多結(jié)點(diǎn)的緊密結(jié)構(gòu),最終變化為更緊密的球狀結(jié)構(gòu).本研究結(jié)果表明奧沙利鉑可通過化學(xué)鍵合作用和靜電作用使質(zhì)粒DNA逐漸凝集為緊密的球狀結(jié)構(gòu),這種結(jié)構(gòu)可能對(duì)奧沙利鉑的抗癌活性和毒性產(chǎn)生重要影響.
[Abstract]:Oxaliplatin is known as the third generation of platinum drugs, especially for gastrointestinal tumors. Most studies show that oxaliplatin is the main target of DNA molecules. However, the key structure and mechanism of the formation of oxaliplatin with DNA molecules are still in the exploring stage. In this study, the interaction of oxaliplatin with DNA in vitro was investigated by UV-Vis absorption spectroscopy and atomic force microscopy (AFM). Cheng. In order to reveal the main molecular structural basis of oxaliplatin to produce anticancer effect. Firstly, the interaction of oxaliplatin with DNA was studied by ultraviolet spectroscopy. On the basis of this, the interaction between oxaliplatin and oxaliplatin was studied. Furthermore, atomic force microscopy (AFM) was used to observe the structure and morphology of oxaliplatin and plasmid DNA at 37 鈩,
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