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人工扩展DNA的实验室进化产生了可重新设计的适体，这些适体靶向炭疽保护性抗原的毒性形式。

Laboratory evolution of artificially expanded DNA gives redesignable aptamers that target the toxic form of anthrax protective antigen.

作者信息

Biondi Elisa, Lane Joshua D, Das Debasis, Dasgupta Saurja, Piccirilli Joseph A, Hoshika Shuichi, Bradley Kevin M, Krantz Bryan A, Benner Steven A

机构信息

Foundation for Applied Molecular Evolution, Alachua, FL 32615, USA.

School of Dentistry, The University of Maryland, Baltimore, MD 21201, USA.

出版信息

Nucleic Acids Res. 2016 Nov 16;44(20):9565-9577. doi: 10.1093/nar/gkw890. Epub 2016 Oct 3.

DOI:10.1093/nar/gkw890
PMID:27701076
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5175368/
Abstract

Reported here is a laboratory in vitro evolution (LIVE) experiment based on an artificially expanded genetic information system (AEGIS). This experiment delivers the first example of an AEGIS aptamer that binds to an isolated protein target, the first whose structural contact with its target has been outlined and the first to inhibit biologically important activities of its target, the protective antigen from Bacillus anthracis We show how rational design based on secondary structure predictions can also direct the use of AEGIS to improve the stability and binding of the aptamer to its target. The final aptamer has a dissociation constant of ∼35 nM. These results illustrate the value of AEGIS-LIVE for those seeking to obtain receptors and ligands without the complexities of medicinal chemistry, and also challenge the biophysical community to develop new tools to analyze the spectroscopic signatures of new DNA folds that will emerge in synthetic genetic systems replacing standard DNA and RNA as platforms for LIVE.

摘要

本文报道了一项基于人工扩展遗传信息系统（AEGIS）的实验室体外进化（LIVE）实验。该实验提供了首个与分离的蛋白质靶标结合的AEGIS适配体实例，首个概述了其与靶标结构接触的实例，以及首个抑制其靶标生物学重要活性的实例，即炭疽芽孢杆菌的保护性抗原。我们展示了基于二级结构预测的合理设计如何也能指导AEGIS的使用，以提高适配体对其靶标的稳定性和结合能力。最终的适配体解离常数约为35 nM。这些结果说明了AEGIS-LIVE对于那些寻求在不涉及药物化学复杂性的情况下获得受体和配体的人的价值，同时也向生物物理界提出挑战，要求开发新工具来分析将在取代标准DNA和RNA作为LIVE平台的合成遗传系统中出现的新DNA折叠的光谱特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d6/5175368/9d5ad39d60e0/gkw890fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d6/5175368/444b050cd6a8/gkw890fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d6/5175368/2f618d61a0d6/gkw890fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d6/5175368/d966e2c396df/gkw890fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d6/5175368/ac79569c3e43/gkw890fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d6/5175368/cb3c9257b835/gkw890fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d6/5175368/3461a205aa12/gkw890fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d6/5175368/9d5ad39d60e0/gkw890fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d6/5175368/444b050cd6a8/gkw890fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d6/5175368/2f618d61a0d6/gkw890fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d6/5175368/d966e2c396df/gkw890fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d6/5175368/ac79569c3e43/gkw890fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d6/5175368/cb3c9257b835/gkw890fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d6/5175368/3461a205aa12/gkw890fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d6/5175368/9d5ad39d60e0/gkw890fig7.jpg

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