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首页> 外文期刊>Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena >HIV-integrase aptamer folds into a parallel quadruplex: a thermodynamic study.
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HIV-integrase aptamer folds into a parallel quadruplex: a thermodynamic study.

机译:HIV整合酶适体折叠成平行四链体:热力学研究。

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摘要

Short guanine-rich sequences have a tendency to form quadruplexes that are stabilized by G-quartets with specific cation coordination. Quadruplexes are part of telomeres at the ends of chromosomes and play an important role in the regulation of gene expression. In addition, there is a strong interest in the therapeutic and biotechnological potential of quadruplex oligonucleotides. The HIV-integrase aptamer, d(GGGT)(4), demonstrated unusually favorable van't Hoff thermodynamics, and based on NMR studies the aptamer was proposed to fold into an antiparallel structure. Here we probed an apparent discrepancy between the NMR structure and the quadruplex topology suggested by circular dichroism (CD). Systematic thermodynamic analyses of d(GGGT)(4) and variants containing sequence modifications or missing specific nucleotides are consistent with a parallel quadruplex fold. CD studies carried out over a wide concentration range did not support a possible structural transition upon increasing strand concentration. Taken together, both optical and thermodynamic studies performed here strongly support a parallel fold for the d(GGGT)(4) aptamer.
机译:富含鸟嘌呤的短序列具有形成四链体的趋势,这些四链体可通过具有特定阳离子配位的G四联体来稳定。四重体是染色体末端的端粒的一部分,在调节基因表达中起重要作用。此外,人们对四链寡核苷酸的治疗和生物技术潜力非常感兴趣。 HIV整合酶适体d(GGGT)(4)表现出异常有利的van't Hoff热力学,并且基于NMR研究,该适体被提议折叠成反平行结构。在这里,我们探究了NMR结构与圆二色性(CD)建议的四链体拓扑之间的明显差异。 d(GGGT)(4)和包含序列修饰或缺失特定核苷酸的变异体的系统热力学分析与平行四链体折叠相符。在较宽的浓度范围内进行的CD研究不支持链浓度增加时可能的结构转变。两者合计,这里进行的光学和热力学研究都强烈支持d(GGGT)(4)适体的平行折叠。

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