Gold L, Polisky B, Uhlenbeck O, Yarus M
NeXstar Pharmaceuticals, Inc., Boulder, Colorado 80301, USA.
Annu Rev Biochem. 1995;64:763-97. doi: 10.1146/annurev.bi.64.070195.003555.
SELEX is a technology for the identification of high affinity oligonucleotide ligands. Large libraries of random sequence single-stranded oligonucleotides, whether RNA or DNA, can be thought of conformationally not as short strings but rather as sequence dependent folded structures with high degrees of molecular rigidity in solution. This conformational complexity means that such a library is a source of high affinity ligands for a surprising variety of molecular targets, including nucleic acid binding proteins such as polymerases and transcription factors, non-nucleic acid binding proteins such as cytokins and growth factors, as well as small organic molecules such as ATP and theophylline. The range of applications of this technology for new discovery extends from basic research reagents to the identification of novel diagnostic and therapeutic reagents. Examples of these applications are described along with a discussion of underlying principles and future developments expected to further the utility of SELEX.
指数富集的配体系统进化技术(SELEX)是一种用于鉴定高亲和力寡核苷酸配体的技术。无论是RNA还是DNA,随机序列单链寡核苷酸的大型文库在构象上不能被视为短链,而应被视为在溶液中具有高度分子刚性的依赖于序列的折叠结构。这种构象复杂性意味着这样的文库是多种分子靶标的高亲和力配体来源,包括核酸结合蛋白如聚合酶和转录因子、非核酸结合蛋白如细胞因子和生长因子,以及小分子有机化合物如ATP和茶碱。该技术在新发现方面的应用范围从基础研究试剂扩展到新型诊断和治疗试剂的鉴定。文中描述了这些应用的实例,并讨论了其基本原理以及有望进一步提升SELEX效用的未来发展。