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.
Highlights
DNA-templated synthesis takes advantage of the programmability of DNA-DNA interactions to accelerate chemical reactions under diluted conditions upon sequence-specific hybridization
The specificity, selectivity, and programmability of DNA–DNA interactions together with the possibility of conjugating different reactive groups to synthetic oligonucleotides have allowed a wide range of chemical reactions to be directed by a variety of templating architectures[23,46]
The advent of synthetic biology together with DNA and aptamer nanotechnology has opened a new route to DNA templated synthesis (DTS) where nucleic acid templated reactions could be used for targeted drug synthesis triggered by specific nucleic acid biomarkers
Summary
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. Artificial molecular containers, defined as “molecular flasks”[10], that are able to modulate the chemical reactivity through confinement, include molecular capsules and boxes[11,12], zeolites[13], covalent organic frameworks[14], and metal–organic frameworks[15,16] Another approach to enhance the reaction rate between reactive species by increasing their effective concentration is based on the use of templates, molecular scaffolds designed to co-localize, and orient reactive units in a confined volume. Triggering DNA-templated reactions with other nonnucleic acid co-templating biomolecules, including relevant clinical biomarkers, would increase both the versatility and utility of DTS and broaden the contexts in which chemical reactivity could be controlled
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