Understanding Nucleic Acids Using Synthetic Chemistry
2004/08/31 by Steven A. Benner · 379 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · #Abiogenesis #Biochemical and Molecular Research #Biochemistry #Biology #Chemistry #Combinatorial chemistry #Computational biology #DNA #DNA and Nucleic Acid Chemistry #Genetics #Materials science #Nanotechnology #Nucleic acid #Nucleobase #RNA and protein synthesis mechanisms #Synthetic biology
paper · doi:10.1021/ar040004z
published in Accounts of Chemical Research 37(10), 784-797 (American Chemical Society)
openalex publication_date 2004/08/31 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/15
Abstract
This Account describes work done in these laboratories that has used synthetic, physical organic, and biological chemistry to understand the roles played by the nucleobases, sugars, and phosphates of DNA in the molecular recognition processes central to genetics. The number of nucleobases has been increased from 4 to 12, generating an artificially expanded genetic information system. This system is used today in the clinic to monitor the levels of HIV and hepatitis C viruses in patients, helping to manage patient care. Work with uncharged phosphate replacements suggests that a repeating charge is a universal feature of genetic molecules operating in water and will be found in extraterrestrial life (if it is ever encountered). The use of ribose may reflect prebiotic processes in the presence of borate-containing minerals, which stabilize ribose formed from simple organic precursors. A new field, synthetic biology, is emerging on the basis of these experiments, where chemistry mimics biological processes as complicated as Darwinian evolution.
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- Ribose Selected as Precursor to Life
- Signatures of a Shadow Biosphere
- Artificial Genetic Systems: Self‐Avoiding DNA in PCR and Multiplexed PCR
- Is there a common chemical model for life in the universe?
- The possibility of alternative microbial life on Earth
- Origins of building blocks of life: A review
- Alternative DNA Base Pairing through Metal Coordination
- Amplification, Mutation, and Sequencing of a Six-Letter Synthetic Genetic System
- Synthetic biology: putting synthesis into biology
- The Drive to Life on Wet and Icy Worlds
- Primitive Genetic Polymers
- A lander mission to probe subglacial water on Saturn׳s moon Enceladus for life
- From the one-carbon amide formamide to RNA all the steps are prebiotically possible
- Synthetic biology
- Synthetic biology. [europepmc]
- Alkaline fluid circulation in ultramafic rocks and formation of nucleotide constituents: a hypothesis. [europepmc]
- Non-natural nucleic acids for synthetic biology. [europepmc]
- Expanded genetic alphabets in the polymerase chain reaction. [europepmc]
- Fluorescent analogs of biomolecular building blocks: design, properties, and applications. [europepmc]
- Primitive genetic polymers. [europepmc]
- Artificial genetic systems: self-avoiding DNA in PCR and multiplexed PCR. [europepmc]
- Setting the stage: the history, chemistry, and geobiology behind RNA. [europepmc]
- Amplification, mutation, and sequencing of a six-letter synthetic genetic system. [europepmc]
- DNA-multichromophore systems. [europepmc]
- Cell-free biology: exploiting the interface between synthetic biology and synthetic chemistry. [europepmc]
- Artificial genetic sets composed of size-expanded base pairs. [europepmc]
- The drive to life on wet and icy worlds. [europepmc]
- On the Origin of the Canonical Nucleobases: An Assessment of Selection Pressures across Chemical and Early Biological Evolution. [europepmc]
- DNA polymerases engineered by directed evolution to incorporate non-standard nucleotides. [europepmc]
- Structural basis for a six nucleotide genetic alphabet. [europepmc]
- The expanded genetic alphabet. [europepmc]
- Exploring the Chemistry of Genetic Information Storage and Propagation through Polymerase Engineering. [europepmc]
- Detecting Darwinism from Molecules in the Enceladus Plumes, Jupiter's Moons, and Other Planetary Water Lagoons. [europepmc]
- Sequence-Selective Formation of Synthetic H-Bonded Duplexes. [europepmc]
- Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides. [europepmc]
- Artificially Expanded Genetic Information Systems for New Aptamer Technologies. [europepmc]
- A synthetic genetic polymer with an uncharged backbone chemistry based on alkyl phosphonate nucleic acids. [europepmc]
- An Aptamer-Nanotrain Assembled from Six-Letter DNA Delivers Doxorubicin Selectively to Liver Cancer Cells. [europepmc]
- Tautomeric Equilibria of Nucleobases in the Hachimoji Expanded Genetic Alphabet. [europepmc]
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