Many strategies have been developed to modulate the biological or biotechnical properties of oligonucleotides by introducing new chemical functionalities or by enhancing their affinity and specificity while restricting their conformational space. Among them, we review our approach consisting of modifications of the 5’-C-position of the nucleoside sugar. This allows the introduction of an additional chemical handle at any position on the nucleotide chain without disturbing the Watson–Crick base-pairing. We show that 5’-C bromo or propargyl convertible nucleotides (CvN) are accessible in pure diastereoisomeric form, either for nucleophilic displacement or for CuAAC conjugation. Alternatively, the 5’-carbon can be connected in a stereo-controlled manner to the phosphate moiety of the nucleotide chain to generate conformationally constrained nucleotides (CNA). These allow the precise control of the sugar/phosphate backbone torsional angles. The consequent modulation of the nucleic acid shape induces outstanding stabilization properties of duplex or hairpin structures in accordance with the preorganization concept. Some biological applications of these distorted oligonucleotides are also described. Effectively, the convertible and the constrained approaches have been merged to create constrained and convertible nucleotides (C₂NA) providing unique tools to functionalize and stabilize nucleic acids.

中文翻译：

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可转换和受限核苷酸：2'-脱氧核糖 5'-C-功能化方法，法式风格


已经开发出许多策略来通过引入新的化学功能或通过增强寡核苷酸的亲和力和特异性同时限制其构象空间来调节寡核苷酸的生物学或生物技术特性。其中，我们回顾了我们的方法，包括核苷糖 5'-C-位置的修饰。这允许在核苷酸链上的任何位置引入额外的化学手柄，而不会干扰沃森-克里克碱基配对。我们表明，5'-C 溴或炔丙基可转换核苷酸 (CvN) 可以以纯非对映异构形式获得，无论是用于亲核置换还是用于 CuAAC 缀合。或者，5'-碳可以以立体控制的方式连接至核苷酸链的磷酸部分以产生构象约束核苷酸(CNA)。这些允许精确控制糖/磷酸主链扭转角。根据预组织概念，随后对核酸形状的调节诱导了双链体或发夹结构的出色稳定特性。还描述了这些扭曲寡核苷酸的一些生物学应用。实际上，可转换方法和受限方法已合并，创建了受限和可转换核苷酸 (C ₂ NA)，为功能化和稳定核酸提供了独特的工具。