The limits of template-directed synthesis with nucleoside-5′-phosphoro(2-methyl)imidazolides
Abstract
In earlier work we have shown that C-rich templates containing isolated A, T or G residues and short oligo(G) sequences can be copied effectively using nucleoside-5'-phosphoro(2-methyl)imidazolides as substrates. We now show that isolated A or T residues within an oligo(G) sequence are a complete block to copying and that an isolated C residue is copied inefficiently. Replication is possible only if there are two complementary oligonucleotides each of which acts as a template to facilitate the synthesis of the other. We emphasize the severity of the problems that need to be overcome to make possible non-enzymatic replication in homogeneous aqueous solution. We conclude that an efficient catalyst was involved in the origin of polynucleotide replication.
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Enzyme-free primer extension initially explored by Orgel and colleagues faced significant limitations, including low yield, prolonged reaction time and poor fidelity.
“Initially explored by Orgel and colleagues to understand the origins of life, this method faced significant limitations, including low yield, prolonged reaction time and poor fidelity.8”
From Sequencing of <scp>d</scp>/<scp>l</scp>-DNA and XNA by Templated-Synthesis (2025) · cites this paper as [8]
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- Authors
- Hill, A. R., Orgel, L. E., & Wu, T.
- Affiliations
- Salk Institute for Biological Studies (US)
- Northwestern University (US)
- Venue
- Origins of life and evolution of the biosphere
- Published
- 1993-12
- Volume
- 23
- Issue
- 5-6
- Pages
- 285-290
- ISSN
- 0169-6149 (ISSN-L)
- 1573-0875
- OpenAlex
- W2065742859
- Cited by
- 92
- References
- 8
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 5 · 2021: 2 · 2020: 1 · 2019: 7 · 2018: 2 · 2017: 2 · 2016: 5 · 2015: 10 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Origins of Life and Evolution of Biospheres (publishedVersion)
- PubMed (publishedVersion)
- NASA STI Repository (National Aeronautics and Space Administration) (submittedVersion)
- Funders
- National Aeronautics and Space Administration
- Topics
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- template synthesis
- MeSH terms
- Base Sequence, DNA, DNA Replication, Models, Biological, Molecular Sequence Data, Nucleic Acid Conformation, Nucleotides, Oligodeoxyribonucleotides
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