CAJ | 학술논문

核酸的多样化功能正在逐渐被揭示出来，从核酶的催化功能，适配体特异性结合靶分子，到小 RNA 分子对于基因的干扰和调控，4种碱基和核糖-磷酸单元骨架借助多样化的高级结构展现出的化学活性和生物活性远非我们现在的认识水平，或许还有更多的功能等待开发出来。从这些天然和非天然功能核酸的结构和机制研究中，碱基替换和消除作为最常用的研究方法，使我们认识到碱基以平面堆积、静电作用、络合作用、氢键，尤其是广义酸碱的方式参与功能结构域的形成和化学反应。自然选择和人工筛选的功能核酸都具有高度的序列保守性，但从10-23脱氧核酶的功能基修饰获得了能提高催化反应速率的修饰位点和先导结构。因此，基于功能基水平的化学修饰，让我们看到了优化功能核酸的可能性，为更好地发挥功能核酸在研究工具和治疗药物方面的潜力带来了希望，虽然对于每一种功能核酸的优化修饰，引入何种功能基和如何引入功能基都是一种挑战。
핵산적다양화공능정재축점피게시출래，종핵매적최화공능，괄배체특이성결합파분자，도소 RNA 분자대우기인적간우화조공，4충감기화핵당-린산단원골가차조다양화적고급결구전현출적화학활성화생물활성원비아문현재적인식수평，혹허환유경다적공능등대개발출래。종저사천연화비천연공능핵산적결구화궤제연구중，감기체환화소제작위최상용적연구방법，사아문인식도감기이평면퇴적、정전작용、락합작용、경건，우기시엄의산감적방식삼여공능결구역적형성화화학반응。자연선택화인공사선적공능핵산도구유고도적서렬보수성，단종10-23탈양핵매적공능기수식획득료능제고최화반응속솔적수식위점화선도결구。인차，기우공능기수평적화학수식，양아문간도료우화공능핵산적가능성，위경호지발휘공능핵산재연구공구화치료약물방면적잠력대래료희망，수연대우매일충공능핵산적우화수식，인입하충공능기화여하인입공능기도시일충도전。
The diversity of functional nucleic acids is being explored from nature and in vitro selections,including ribozyme catalysis,aptamer binding to target molecules with high specific and affinity,and RNA interference and modulation of gene expression. The great potential of chemical and biological activity of four nucleobases and the sugar-phosphate backbone in various specific tertiary structures is beyond our present imagination,and more functions remain to be found. Therefore,developing insight into the structural basis of these functional nucleic acids is invaluable in understanding their mechanisms and exploring the applications. With a special focus on the four nucleobases,we learnt that nucleobases could contribute to the functions by base stacking,electrostatic interactions,complexion with metal ions,hydrogen bonding,and even act as general acid-base in specific functions. Deletion and substitution of each nucleobases demonstrated the conservation of all the natural and unnatural functional nucleic acids. But from the success of chemical modifications at the level of functional groups on 10-23 DNAzyme,there is still room for the optimization of functional nucleic acids,for practical applications as research tools and genetic therapeutics. It is a big challenge for any functional nucleic acids,to conduct the chemical modification in a right way in the complex tertiary structures, including which residue could be used for chemical modification and which functional groups could be introduced for an expected positive effect.