Engineering DNA Crystals toward Studying DNA-Guest Molecule Interactions.
Engineering DNA Crystals toward Studying DNA-Guest Molecule Interactions.
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DOI：
10.1021/jacs.3c00081
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发表时间：
2023-02
影响因子：
15
通讯作者：
Cuizheng Zhang;Jiemin Zhao;Brandon Lu;N. Seeman;R. Sha;N. Noinaj;C. Mao
中科院分区：
文献类型：
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作者：
Cuizheng Zhang;Jiemin Zhao;Brandon Lu;N. Seeman;R. Sha;N. Noinaj;C. Mao
DNA双链体的序列选择性识别对于包括调节基因表达、药物开发和基因组编辑在内的广泛应用是重要的。许多小分子可以以序列选择性结合DNA双链体。如何可靠方便地获得DNA-分子相互作用的详细结构信息仍然是一个挑战，因为这些信息对于理解DNA-分子相互作用的基本规则至关重要。如果这些规则被理解，我们可以设计分子来识别具有序列偏好的DNA双链体，并干预相关的生物过程，例如疾病治疗。在这里，我们已经证明了DNA晶体工程是一个潜在的解决方案。分子结合DNA序列被设计成自组装成高度有序的DNA晶体。分子-DNA共晶体的X射线晶体学研究揭示了分子如何与DNA双链体相互作用的结构细节。在这种方法中，DNA将发挥两种功能：（1）成为待研究分子的一部分;（2）形成晶格。可以想象，这种方法将是研究药物/肽-DNA相互作用的通用方法。所得的DNA晶体也可以用作分离基质，作为催化剂的宿主，以及作为材料储存的介质。
Sequence-selective recognition of DNA duplexes is important for a wide range of applications including regulating gene expression, drug development, and genome editing. Many small molecules can bind DNA duplexes with sequence selectivity. It remains as a challenge how to reliably and conveniently obtain the detailed structural information on DNA-molecule interactions because such information is critically needed for understanding the underlying rules of DNA-molecule interactions. If those rules were understood, we could design molecules to recognize DNA duplexes with a sequence preference and intervene in related biological processes, such as disease treatment. Here, we have demonstrated that DNA crystal engineering is a potential solution. A molecule-binding DNA sequence is engineered to self-assemble into highly ordered DNA crystals. An X-ray crystallographic study of molecule-DNA cocrystals reveals the structural details on how the molecule interacts with the DNA duplex. In this approach, the DNA will serve two functions: (1) being part of the molecule to be studied and (2) forming the crystal lattice. It is conceivable that this method will be a general method for studying drug/peptide-DNA interactions. The resulting DNA crystals may also find use as separation matrices, as hosts for catalysts, and as media for material storage.