Understanding the mechanism by which biological macromolecules fold into their functional native conformations represents a problem of fundamental interest. DNA oligonucleotides derived from human telomeric repeat d[TAGGG(TTAGGG)3] and d[TAGGG(TTAGGG)3TT] fold into G-quadruplexes through diverse steps. Varying the pH and temperature by the use of nuclear magnetic resonance and other methods enabled detection of pre-folded structures that exist in solution before completely formed G-quadruplexes upon addition of cations. Pre-folded structures are in general hard to detect, however their knowledge is crucial to set up folding pathways into final structure since they are believed to be a starting point. Unexpectedly well-defined pre-folded structures composed of base triples for both oligonucleotides were detected at certain pH and temperature. These kinds of structures were up to now only hypothesized as intermediates in the folding process. All revealed pre-folded structures irrespective of the pH and temperature exhibited one common structural feature that could govern folding process.

中文翻译：

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预折叠的结构控制着人类端粒G-四链体的折叠途径。

理解生物大分子折叠成其功能性天然构象的机制代表了一个基本的问题。源自人类端粒重复序列d [TAGGG（TTAGGG）3]和d [TAGGG（TTAGGG）3TT]的DNA寡核苷酸通过不同的步骤折叠成G-四链体。通过使用核磁共振和其他方法改变pH和温度，可以检测到存在于溶液中的预折叠结构，然后在添加阳离子后完全形成G-四链体。预折叠结构通常很难检测，但是，由于它们被认为是起点，因此它们的知识对于将折叠路径建立为最终结构至关重要。在某些pH和温度下，检测到了由两个寡核苷酸的碱基三元组成的预定义良好的预折叠结构。到目前为止，这类结构仅被假设为折叠过程中的中间体。所有揭示的预折叠结构，无论pH和温度如何，均表现出一种可控制折叠过程的共同结构特征。