ArticleJournal of the American Chemical Society2013
Expanding the scope of replicable unnatural DNA: stepwise optimization of a predominantly hydrophobic base pair.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- 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
- A Closer Look at Non-random Patterns Within Chemistry Space for a Smaller, Earlier Amino Acid Alphabet.Journal of molecular evolution · 2022Article
- Genetic Code Engineering by Natural and Unnatural Base Pair Systems for the Site-Specific Incorporation of Non-Standard Amino Acids Into Proteins.Frontiers in molecular biosciences · 2022Review
- Synthesis ofChemical science · 2021Article
- Diastereoselective Synthesis of Aryl C-Glycosides from Glycosyl Esters via C-O Bond Homolysis.Angewandte Chemie (International ed. in English) · 2021Article
- Progress Toward a Semi-Synthetic Organism with an Unrestricted Expanded Genetic Alphabet.Journal of the American Chemical Society · 2018Article
- Expansion of the Genetic Alphabet: A Chemist's Approach to Synthetic Biology.Accounts of chemical research · 2018Article
- In Vivo Structure-Activity Relationships and Optimization of an Unnatural Base Pair for Replication in a Semi-Synthetic Organism.Journal of the American Chemical Society · 2017Article
- NAngewandte Chemie (International ed. in English) · 2017Article
- Laboratory evolution of artificially expanded DNA gives redesignable aptamers that target the toxic form of anthrax protective antigen.Nucleic acids research · 2016Article
- The Toolbox for Modified Aptamers.Molecular biotechnology · 2016Review
- The expanded genetic alphabet.Angewandte Chemie (International ed. in English) · 2015Review
- DNA based multi-copper ions assembly using combined pyrazole and salen ligandosides.Chemical science · 2015Article
- Natural-like replication of an unnatural base pair for the expansion of the genetic alphabet and biotechnology applications.Journal of the American Chemical Society · 2014Article
- Systematic exploration of a class of hydrophobic unnatural base pairs yields multiple new candidates for the expansion of the genetic alphabet.Nucleic acids research · 2014Article
- Artificial genetic sets composed of size-expanded base pairs.Angewandte Chemie (International ed. in English) · 2013Review
- Site-specifically arraying small molecules or proteins on DNA using an expanded genetic alphabet.Chemistry (Weinheim an der Bergstrasse, Germany) · 2013Article
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Authors and funding
7 authors.
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Abstract
As part of an ongoing effort to expand the genetic alphabet for in vitro and eventually in vivo applications, we have synthesized a wide variety of predominantly hydrophobic unnatural base pairs exemplified by d5SICS-dMMO2 and d5SICS-dNaM. When incorporated into DNA, the latter is replicated and transcribed with greater efficiency and fidelity than the former; however, previous optimization efforts identified the para and methoxy-distal meta positions of dMMO2 as particularly promising for further optimization. Here, we report the stepwise optimization of dMMO2 via the synthesis and evaluation of 18 novel para-derivatized analogs of dMMO2, followed by further derivatization and evaluation of the most promising analogs with meta substituents. Subject to size constraints, we find that para substituents can optimize replication via both steric and electronic effects and that meta methoxy groups are unfavorable, while fluoro substituents can be beneficial or deleterious depending on the para substituent. In addition, we find that improvements in the efficiency of unnatural triphosphate insertion translate most directly into higher fidelity replication. Importantly, we identify multiple, unique base pair derivatives that when incorporated into DNA are well replicated. The most promising, d5SICS-dFEMO, is replicated under some conditions with greater efficiency and fidelity than d5SICS-dNaM. These results clearly demonstrate the generality of hydrophobic forces for the control of base pairing within DNA, provide a wealth of new SAR data, and importantly identify multiple new candidates for eventual in vivo evaluation.
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