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核酸适配体（aptamer）是通过指数富集配体系统进化（SELEX）技术筛选得到的核糖核酸（RNA）或单链脱氧核糖核酸（ ssDNA）。核酸适配体通过高亲和力特异性地识别小分子、蛋白质、细胞、微生物等多种靶标，在生物、医药、食品和环境检测等领域的应用日渐增多。但目前实际可用的核酸适配体有限，其筛选过程复杂，筛选难度大，制约了其应用。与生物大分子、细胞和微生物等靶标不同，小分子靶标与核酸分子的结合位点少、亲和力弱，且靶标通常需要固定在载体上。此外，小分子靶标结合核酸形成的复合物与核酸自身的大小、质量、电荷性质等方面差异较小，二者的分离难度大。故小分子靶标的核酸适配体筛选过程与大分子和细胞等复合靶标相比有明显差异，筛选难度更大。因此需要根据其自身结构特点和核酸适配体的应用目的选定靶标或核酸库的固定方法，优化靶标核酸复合物的分离方法。本文介绍了不同类型小分子（具有基团差异的单分子、含相同基团分子和手性分子等）靶标的选择及其核酸适配体的筛选方法，并对核酸库的设计、与靶标结合的核酸的分离方法和亲和作用表征方法进行了介绍，列出了自2008年以来报道的40余种小分子靶标的核酸适配体序列和复合物的平衡解离常数（Kd）。

Aptamers are ribonucleic acid ( RNA ) or single-stranded deoxyribonucleic acid ( ssDNA ) selected by systematic evolution of ligands by exponential enrichment ( SELEX ). Aptamers can identify small molecules,proteins,cells,microorganisms and other targets with high affinity and specificity,and have been widely applied in biology,medicine,food and environmental monitoring. However,available aptamers of practical use are limited. The com-plex and difficult screening of aptamers are the key to restrict its wide application. Differing from biomacromolecules,cells and microorganisms,small molecules have less binding sites and weaker affinity with nucleic acids. And they usually need to be immobilized on substrates. In addition,due to the tiny differences of size,weight and charge of the target-ssDNA/RNA complex and ssDNA/RNA,their separation is difficult. Therefore,the aptamer selection of small molecules is more difficult than biomacromolecules or cells. The selection of methods for immobilizing the targets or library and the optimization of separation process proceed mainly based on the structure characteristics and applications of aptamers. In this paper,the screening methods for molecules with different groups,molecules containing the same group and chiral molecules are introduced. Also,the library design,the methods for separating targets-ssDNA complex and characterizing affinity interaction are discussed. The sequences and dissociation constants(Kd)of about 40 aptamers reported since 2008 are listed.