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核心技术专利:CN118964589B侵权必究
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用于将多种输入转化为可编程输出的共价动态DNA网络。

Covalent Dynamic DNA Networks to Translate Multiple Inputs into Programmable Outputs.

作者信息

Brannetti Simone, Gentile Serena, Del Grosso Erica, Otto Sijbren, Ricci Francesco

机构信息

Department of Chemical Sciences and Technologies, University of Rome, Tor Vergata, Via della Ricerca Scientifica, Rome 00133, Italy.

Centre for Systems Chemistry, Stratingh Institute, University of Groningen, Groningen 9747 AG, Netherlands.

出版信息

J Am Chem Soc. 2025 Feb 19;147(7):5755-5763. doi: 10.1021/jacs.4c13854. Epub 2025 Feb 5.


DOI:10.1021/jacs.4c13854
PMID:39905964
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11848822/
Abstract

Inspired by naturally occurring protein dimerization networks, in which a set of proteins interact with each other to achieve highly complex input-output behaviors, we demonstrate here a fully synthetic DNA-based dimerization network that enables highly programmable input-output computations. Our DNA-based dimerization network consists of DNA oligonucleotide monomers modified with reactive moieties that can covalently bond with each other to form dimer outputs in an all-to-all or many-to-many fashion. By designing DNA-based input strands that can specifically sequester DNA monomers, we can control the size of the reaction network and thus fine-tune the yield of each DNA dimer output in a predictable manner. Thanks to the programmability and specificity of DNA-DNA interactions, we show that this approach can be used to control the yield of different dimer outputs using different inputs. The approach is also versatile and we demonstrate dimerization networks based on two distinct covalent reactions: thiol-disulfide and strain-promoted azide-alkyne cycloaddition (SPAAC) reactions. Finally, we show here that the DNA-based dimerization network can be used to control the yield of a functional dimer output, ultimately controlling the assembly and disassembly of DNA nanostructures. The covalent dynamic DNA networks shown here provide a way to convert multiple inputs into programmable outputs that can control a broader range of functions, including ones that mimic those of living cells.

摘要

受天然存在的蛋白质二聚化网络的启发,在该网络中一组蛋白质相互作用以实现高度复杂的输入-输出行为,我们在此展示了一种完全基于合成DNA的二聚化网络,它能够进行高度可编程的输入-输出计算。我们基于DNA的二聚化网络由用反应性基团修饰的DNA寡核苷酸单体组成,这些单体可以彼此共价结合,以全对全或多对多的方式形成二聚体输出。通过设计能够特异性隔离DNA单体的基于DNA的输入链,我们可以控制反应网络的大小,从而以可预测的方式微调每个DNA二聚体输出的产量。由于DNA-DNA相互作用的可编程性和特异性,我们表明这种方法可用于使用不同输入来控制不同二聚体输出的产量。该方法也具有通用性,我们展示了基于两种不同共价反应的二聚化网络:硫醇-二硫键和应变促进的叠氮化物-炔烃环加成(SPAAC)反应。最后,我们在此表明基于DNA的二聚化网络可用于控制功能性二聚体输出的产量,最终控制DNA纳米结构的组装和拆卸。此处展示的共价动态DNA网络提供了一种将多个输入转换为可编程输出的方法,这些输出可以控制更广泛的功能,包括那些模仿活细胞功能的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4075/11848822/60e2b8b68811/ja4c13854_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4075/11848822/930f2e33c128/ja4c13854_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4075/11848822/8cea16ea454f/ja4c13854_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4075/11848822/a616779269d2/ja4c13854_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4075/11848822/60e2b8b68811/ja4c13854_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4075/11848822/930f2e33c128/ja4c13854_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4075/11848822/8cea16ea454f/ja4c13854_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4075/11848822/a616779269d2/ja4c13854_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4075/11848822/60e2b8b68811/ja4c13854_0004.jpg

相似文献

[1]
Covalent Dynamic DNA Networks to Translate Multiple Inputs into Programmable Outputs.

J Am Chem Soc. 2025-2-19

[2]
Optimizing the selectivity of DIFO-based reagents for intracellular bioorthogonal applications.

Carbohydr Res. 2013-5-28

[3]
Preventing thiol-yne addition improves the specificity of strain-promoted azide-alkyne cycloaddition.

Bioconjug Chem. 2012-3-8

[4]
Interfacial strain-promoted alkyne-azide cycloaddition (I-SPAAC) for the synthesis of nanomaterial hybrids.

Chem Commun (Camb). 2013-4-3

[5]
Azidopropylvinylsulfonamide as a New Bifunctional Click Reagent for Bioorthogonal Conjugations: Application for DNA-Protein Cross-Linking.

Chemistry. 2015-11-2

[6]
From mechanism to mouse: a tale of two bioorthogonal reactions.

Acc Chem Res. 2011-8-15

[7]
Facile Quenching and Spatial Patterning of Cylooctynes via Strain-Promoted Alkyne-Azide Cycloaddition of Inorganic Azides.

Bioconjug Chem. 2017-5-17

[8]
Strain-promoted "click" chemistry for terminal labeling of DNA.

Bioconjug Chem. 2011-6-2

[9]
Strain-promoted azide-alkyne cycloaddition for protein-protein coupling in the formation of a bis-hemoglobin as a copper-free oxygen carrier.

Org Biomol Chem. 2016-10-25

[10]
Accelerating Strain-Promoted Azide-Alkyne Cycloaddition Using Micellar Catalysis.

Bioconjug Chem. 2015-8-19

本文引用的文献

[1]
Contextual computation by competitive protein dimerization networks.

Cell. 2025-4-3

[2]
Competitive exclusion among self-replicating molecules curtails the tendency of chemistry to diversify.

Nat Chem. 2025-1

[3]
DNA as a universal chemical substrate for computing and data storage.

Nat Rev Chem. 2024-3

[4]
Combinatorial expression motifs in signaling pathways.

Cell Genom. 2024-1-10

[5]
Light-driven eco-evolutionary dynamics in a synthetic replicator system.

Nat Chem. 2024-1

[6]
DNA-Based Signaling Networks for Transient Colloidal Co-Assemblies.

J Am Chem Soc. 2023-8-16

[7]
The computational capabilities of many-to-many protein interaction networks.

Cell Syst. 2023-6-21

[8]
Molecular Computation for Molecular Classification.

Adv Biol (Weinh). 2023-3

[9]
Multimodal perception links cellular state to decision-making in single cells.

Science. 2022-8-5

[10]
The E-Id Axis Instructs Adaptive Versus Innate Lineage Cell Fate Choice and Instructs Regulatory T Cell Differentiation.

Front Immunol. 2022

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