DNA‐Templated Organic Synthesis: Nature's Strategy for Controlling Chemical Reactivity Applied to Synthetic Molecules
Abstract
In contrast to the approach commonly taken by chemists, nature controls chemical reactivity by modulating the effective molarity of highly dilute reactants through macromolecule‐templated synthesis. Nature's approach enables complex mixtures in a single solution to react with efficiencies and selectivities that cannot be achieved in conventional laboratory synthesis. DNA‐templated organic synthesis (DTS) is emerging as a surprisingly general way to control the reactivity of synthetic molecules by using nature's effective‐molarity‐based approach. Recent developments have expanded the scope and capabilities of DTS from its origins as a model of prebiotic nucleic acid replication to its current ability to translate DNA sequences into complex small‐molecule and polymer products of multistep organic synthesis. An understanding of fundamental principles underlying DTS has played an important role in these developments. Early applications of DTS include nucleic acid sensing, small‐molecule discovery, and reaction discovery with the help of translation, selection, and amplification methods previously available only to biological molecules.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Several DNA-templated reactions with longer probes proceed within minutes at very low concentrations, benefiting from high effective concentrations in stable hybridization complexes.
“In contrast, several DNA-templated reactions with longer probes have been shown to proceed within minutes at very low concentrations, benefiting from high effective concentrations in stable hybridization complexes.18−20”
From Sequencing of <scp>d</scp>/<scp>l</scp>-DNA and XNA by Templated-Synthesis (2025) · cites this paper as [18]
Cites
Design and self-assembly of two-dimensional DNA crystals
Winfree, E., Liu, F., Wenzler, L. A., & Seeman, N. C. (1998) · Nature · doi:10.1038/28998 · Cited by 2,857 · see citing works
The antiquity of RNA-based evolution.
Joyce, G. F. (2002) · Nature · doi:10.1038/418214a · Cited by 1,070 · see citing works
Logical computation using algorithmic self-assembly of DNA triple-crossover molecules
Mao, C., LaBean, T. H., Reif, J. H., & Seeman, N. C. (2000) · Nature · doi:10.1038/35035038 · Cited by 779 · see citing works
Chiral selection in poly(C)-directed synthesis of oligo(G)
Joyce, G. F., Visser, G. M., van Boeckel, C. A. A., van Boom, J. H., Orgel, L. E., & van Westrenen, J. (1984) · Nature · doi:10.1038/310602a0 · Cited by 398 · see citing works
Autocatalytic synthesis of a tetranucleotide analogue
Zielinski, W. S., & Orgel, L. E. (1987) · Nature · doi:10.1038/327346a0 · Cited by 310 · see citing works
Bolli, M., Micura, R., & Eschenmoser, A. (1997) · Chemistry & Biology · doi:10.1016/s1074-5521(97)90074-0 · Cited by 290 · see citing works
Studies in prebiotic synthesis
Fuller, W. D., Sanchez, R. A., & Orgel, L. E. (1972) · Journal of Molecular Biology · doi:10.1016/0022-2836(72)90383-x · Cited by 280 · see citing works
Wu, T., & Orgel, L. E. (1992) · Journal of the American Chemical Society · doi:10.1021/ja00047a001 · Cited by 103 · see citing works
Template-directed synthesis on the pentanucleotide CpCpGpCpC
Inoue, T., Joyce, G. F., Grzeskowiak, K., Orgel, L. E., Brown, J. M., & Reese, C. B. (1984) · Journal of Molecular Biology · doi:10.1016/0022-2836(84)90244-4 · Cited by 80 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Principles and Applications of Nucleic Acid Strand Displacement Reactions
Simmel, F. C., Yurke, B., & Singh, H. R. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00580 · Cited by 792 · see citing works
Small molecules: the missing link in the central dogma
Schreiber, S. L. (2005) · Nature Chemical Biology · doi:10.1038/nchembio0705-64 · Cited by 306 · see citing works
Prebiotically plausible mechanisms increase compositional diversity of nucleic acid sequences
Derr, J., Manapat, M. L., Rajamani, S., Leu, K., Xulvi-Brunet, R., Joseph, I., Nowak, M. A., & Chen, I. A. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks065 · Cited by 74 · see citing works
Chang, D., Lindberg, E., & Winssinger, N. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.6b12764 · Cited by 72 · see citing works
Kim, K. T., & Winssinger, N. (2020) · Chemical Science · doi:10.1039/d0sc00741b · Cited by 17 · see citing works
Rojas Stütz, J. A., & Richert, C. (2006) · Chemistry – A European Journal · doi:10.1002/chem.200501008 · Cited by 9 · see citing works
Sequencing of <scp>d</scp>/<scp>l</scp>-DNA and XNA by Templated-Synthesis
Joshi, S., Romanens, P., & Winssinger, N. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c00708 · Cited by 4 · see citing works
- Authors
- Li, X., & Liu, D. R.
- Affiliations
- Harvard University (US)
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2004-09-16
- Volume
- 43
- Issue
- 37
- Pages
- 4848-4870
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W2106132690
- Cited by
- 538
- References
- 9
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 12 · 2023: 17 · 2022: 17 · 2021: 13 · 2020: 27 · 2019: 19 · 2018: 18 · 2017: 37 · 2016: 20 · 2015: 26 · 2014: 30 · 2013: 32 · 2012: 36
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM065865)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Physical Sciences › Chemistry › Organic Chemistry › Supramolecular Chemistry and Complexes
- Keywords
- effective molarity, nucleic acid sensing, small molecule drug discovery, reaction discovery, multistep organic synthesis, polymer synthesis
- MeSH terms
- Chemistry, Organic, DNA, Polymers, RNA, Templates, Genetic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review