ArticleJournal of the American Chemical Society2009
Optimization of an unnatural base pair toward natural-like replication.
Article in Journal of the American Chemical Society, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- Derivatives of dPMTO, dMTMO, and dTPT3 as efficient genetic alphabets for artificial DNA.Journal of molecular modeling · 2026Article
- High-resolution melting analysis for rapid and cost-effective detection of unnatural base pairs.Biodesign research · 2026Article
- Heck-type C-glycosylations in the synthesis of artificial nucleotides and functional nucleic acids.RSC chemical biology · 2026Review
- Omega Nucleic Acids (ΩNA), Ultimate Nucleic Acids for Future Technology.Molecules (Basel, Switzerland) · 2026Review
- An unnatural base pair for the detection of epigenetic cytosine modifications in DNA.Nature chemistry · 2025Article
- Cracking the Code: Reprogramming the Genetic Script in Prokaryotes and Eukaryotes to Harness the Power of Noncanonical Amino Acids.Chemical reviews · 2024Review
- Engineering tRNAs for the Ribosomal Translation of Non-proteinogenic Monomers.Chemical reviews · 2024Review
- Artificial Small Molecules as Cofactors and Biomacromolecular Building Blocks in Synthetic Biology: Design, Synthesis, Applications, and Challenges.Molecules (Basel, Switzerland) · 2023Review
- Locating, tracing and sequencing multiple expanded genetic letters in complex DNA context via a bridge-base approach.Nucleic acids research · 2023Article
- The Expanded Central Dogma: Genome Resynthesis, Orthogonal Biosystems, Synthetic Genetics.Annual review of biophysics · 2023Review
- Discovery, implications and initial use of semi-synthetic organisms with an expanded genetic alphabet/code.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- From polymerase engineering to semi-synthetic life: artificial expansion of the central dogma.RSC chemical biology · 2022Review
- Preparation of Site-Specifically Spin-Labeled RNA by in Vitro Transcription Using an Expanded Genetic Alphabet.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Strategies for Covalent Labeling of Long RNAs.Chembiochem : a European journal of chemical biology · 2021Review
- Method for Rapid Analysis of Mutant RNA Polymerase Activity on Templates Containing Unnatural Nucleotides.International journal of molecular sciences · 2021Article
- Reprogramming the genetic code.Nature reviews. Genetics · 2021Review
- Bioorthogonal chemistry-based RNA labeling technologies: evolution and current state.Chemical communications (Cambridge, England) · 2020Article
- Posttranscriptional site-directed spin labeling of large RNAs with an unnatural base pair system under non-denaturing conditions.Chemical science · 2020Article
- Site-specific covalent labeling of large RNAs with nanoparticles empowered by expanded genetic alphabet transcription.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Structural Basis for Processing of Unnatural Base Pairs by DNA Polymerases.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Predominantly hydrophobic unnatural nucleotides that selectively pair within duplex DNA as well as during polymerase-mediated replication have recently received much attention as the cornerstone of efforts to expand the genetic alphabet. We recently reported the results of a screen and subsequent lead hit optimization that led to identification of the unnatural base pair formed between the nucleotides dMMO2 and d5SICS. This unnatural base pair is replicated by the Klenow fragment of Escherichia coli DNA polymerase I with better efficiency and fidelity than other candidates reported in the literature. However, its replication remains significantly less efficient than a natural base pair, and further optimization is necessary for its practical use. To better understand and optimize the slowest step of replication of the unnatural base pair, the insertion of dMMO2 opposite d5SICS, we synthesized two dMMO2 derivatives, d5FM and dNaM, which differ from the parent nucleobase in terms of shape, hydrophobicity, and polarizability. We find that both derivatives are inserted opposite d5SICS more efficiently than dMMO2 and that overall the corresponding unnatural base pairs are generally replicated with higher efficiency and fidelity than the pair between dMMO2 and d5SICS. In fact, in the case of the dNaM:d5SICS heteropair, the efficiency of each individual step of replication approaches that of a natural base pair, and the minimum overall fidelity ranges from 10(3) to 10(4). In addition, the data allow us to propose a generalized model of unnatural base pair replication, which should aid in further optimization of the unnatural base pair and possibly in the design of additional unnatural base pairs that are replicated with truly natural-like efficiency and fidelity.
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