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利用抗体控制基于 DNA 模板的化学反应。

Using antibodies to control DNA-templated chemical reactions.

机构信息

Chemistry Department, University of Rome, Tor Vergata, Via della Ricerca Scientifica, 00133, Rome, Italy.

ATDBio Ltd, Magdalen Centre, Oxford Science Park, Robert Robinson Avenue, Oxford, OX4 4GA, UK.

出版信息

Nat Commun. 2020 Dec 7;11(1):6242. doi: 10.1038/s41467-020-20024-3.

DOI:10.1038/s41467-020-20024-3
PMID:33288745
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7721721/
Abstract

DNA-templated synthesis takes advantage of the programmability of DNA-DNA interactions to accelerate chemical reactions under diluted conditions upon sequence-specific hybridization. While this strategy has proven advantageous for a variety of applications, including sensing and drug discovery, it has been so far limited to the use of nucleic acids as templating elements. Here, we report the rational design of DNA templated synthesis controlled by specific IgG antibodies. Our approach is based on the co-localization of reactants induced by the bivalent binding of a specific IgG antibody to two antigen-conjugated DNA templating strands that triggers a chemical reaction that would be otherwise too slow under diluted conditions. This strategy is versatile, orthogonal and adaptable to different IgG antibodies and can be employed to achieve the targeted synthesis of clinically-relevant molecules in the presence of specific IgG biomarker antibodies.

摘要

DNA 模板合成利用 DNA-DNA 相互作用的可编程性,在序列特异性杂交后,在稀释条件下加速化学反应。虽然该策略已被证明在多种应用中具有优势,包括传感和药物发现,但迄今为止仅限于将核酸用作模板元件。在这里,我们报告了受特定 IgG 抗体控制的 DNA 模板合成的合理设计。我们的方法基于两种抗原偶联的 DNA 模板链的双价结合诱导的反应物的共定位,这触发了一种化学反应,如果在稀释条件下反应速度太慢,则无法进行该反应。该策略具有多功能性、正交性和适应性,可以与不同的 IgG 抗体结合使用,并可用于在存在特定 IgG 生物标志物抗体的情况下实现临床相关分子的靶向合成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0add/7721721/f6de753156e4/41467_2020_20024_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0add/7721721/4199446bb8bb/41467_2020_20024_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0add/7721721/5d9e84d84bc5/41467_2020_20024_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0add/7721721/4f811ee0318d/41467_2020_20024_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0add/7721721/082e5fce444e/41467_2020_20024_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0add/7721721/f6de753156e4/41467_2020_20024_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0add/7721721/4199446bb8bb/41467_2020_20024_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0add/7721721/5d9e84d84bc5/41467_2020_20024_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0add/7721721/4f811ee0318d/41467_2020_20024_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0add/7721721/082e5fce444e/41467_2020_20024_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0add/7721721/f6de753156e4/41467_2020_20024_Fig5_HTML.jpg

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