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寡核苷酸功能的多样性。

Diversity of oligonucleotide functions.

作者信息

Gold L, Polisky B, Uhlenbeck O, Yarus M

机构信息

NeXstar Pharmaceuticals, Inc., Boulder, Colorado 80301, USA.

出版信息

Annu Rev Biochem. 1995;64:763-97. doi: 10.1146/annurev.bi.64.070195.003555.

DOI:10.1146/annurev.bi.64.070195.003555
PMID:7574500
Abstract

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.

摘要

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。

相似文献

1
Diversity of oligonucleotide functions.寡核苷酸功能的多样性。
Annu Rev Biochem. 1995;64:763-97. doi: 10.1146/annurev.bi.64.070195.003555.
2
Mirror-design of L-oligonucleotide ligands binding to L-arginine.与L-精氨酸结合的L-寡核苷酸配体的镜像设计。
Nat Biotechnol. 1996 Sep;14(9):1116-9. doi: 10.1038/nbt0996-1116.
3
Control of complexity constraints on combinatorial screening for preferred oligonucleotide hybridization sites on structured RNA.对结构化RNA上优选寡核苷酸杂交位点的组合筛选中复杂性约束的控制
Biochemistry. 1997 Apr 22;36(16):5004-19. doi: 10.1021/bi9620767.
4
Two sides of the coin: affinity and specificity of nucleic acid interactions.事物的两面性:核酸相互作用的亲和力和特异性。
Trends Biochem Sci. 2004 Feb;29(2):62-71. doi: 10.1016/j.tibs.2003.12.007.
5
Isolation and characterization of 2'-fluoro-, 2'-amino-, and 2'-fluoro-/amino-modified RNA ligands to human IFN-gamma that inhibit receptor binding.
J Immunol. 1997 Jul 1;159(1):259-67.
6
Rapid isolation of high-affinity protein binding peptides using bacterial display.利用细菌展示技术快速分离高亲和力蛋白质结合肽
Protein Eng Des Sel. 2004 Oct;17(10):731-9. doi: 10.1093/protein/gzh084. Epub 2004 Nov 5.
7
Technology evaluation: SELEX, Gilead Sciences Inc.
Curr Opin Mol Ther. 2000 Feb;2(1):100-5.
8
Shape space. Is biopharmaceutical discovery entering a new evolutionary stage?
Biotechnology (N Y). 1993 Mar;11(3):285-9. doi: 10.1038/nbt0393-285.
9
Exploring molecular diversity with combinatorial shape libraries.利用组合形状文库探索分子多样性。
Trends Biochem Sci. 1994 Feb;19(2):57-64. doi: 10.1016/0968-0004(94)90033-7.
10
[Molecular evolution: creation of nucleic acids capable of specific complex formation and possessing catalytic functions].[分子进化:能够形成特异性复合物并具有催化功能的核酸的产生]
Mol Biol (Mosk). 1993 Jan-Feb;27(1):5-13.

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