DNA display III. Solid-phase organic synthesis on unprotected DNA.
DNA display III. Solid-phase organic synthesis on unprotected DNA.
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DOI：
10.1371/journal.pbio.0020175
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发表时间：
2004-07
期刊：
影响因子：
9.8
通讯作者：
Harbury PB
中科院分区：
文献类型：
--
作者：
Halpin DR;Lee JA;Wrenn SJ;Harbury PB
DNA定向合成代表了分子发现的强大新工具。然而，它的最终用途取决于在未受保护的DNA存在下可以执行的化学反应的多样性。我们提出了一种固相反应的格式，使得可能使用标准的有机反应条件和常见的试剂，以促进未保护的DNA支持上的化学转化。我们证明了这种策略的可行性，通过全面适应固相9-芴基甲氧基羰基为基础的肽合成DNA兼容，我们描述了一套工具，用于适应其他化学。有效的肽偶联DNA观察到所有33个氨基酸的测试，和多肽，只要12个氨基酸的DNA支持合成。除了对肽-DNA缀合物的合成的直接影响之外，所描述的方法提供了在未保护的DNA上进行有机合成的一般策略。它们的就业可以促进化学多样性的DNA编码的分子群体的产生，适合于体外进化和遗传操作。提出了一种方法，该方法使得在未保护的DNA存在下使用标准有机反应条件和常用试剂成为可能，这是使DNA指导的化学合成和药物发现成为可能的重要步骤
DNA-directed synthesis represents a powerful new tool for molecular discovery. Its ultimate utility, however, hinges upon the diversity of chemical reactions that can be executed in the presence of unprotected DNA. We present a solid-phase reaction format that makes possible the use of standard organic reaction conditions and common reagents to facilitate chemical transformations on unprotected DNA supports. We demonstrate the feasibility of this strategy by comprehensively adapting solid-phase 9-fluorenylmethyoxycarbonyl–based peptide synthesis to be DNA-compatible, and we describe a set of tools for the adaptation of other chemistries. Efficient peptide coupling to DNA was observed for all 33 amino acids tested, and polypeptides as long as 12 amino acids were synthesized on DNA supports. Beyond the direct implications for synthesis of peptide–DNA conjugates, the methods described offer a general strategy for organic synthesis on unprotected DNA. Their employment can facilitate the generation of chemically diverse DNA-encoded molecular populations amenable to in vitro evolution and genetic manipulation. A method is presented that makes possible the use of standard organic reaction conditions and common reagents in the presence of unprotected DNA, an important step in enabling DNA-directed chemical synthesis and drug discovery
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