Supernatural: Artificial Nucleobases and Backbones to Program Hybridization-Based Assemblies and Circuits

López-Tena, Miguel; Chen, Si-Kai; Winssinger, Nicolas

doi:10.1021/acs.bioconjchem.2c00292

Cited by 8 publications

(15 citation statements)

References 153 publications

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“…A large range of artificial nucleobases and backbones have been developed enabling the diversification of the standard "four-letter alphabet". [47,48] Hili et al developed the Ligasecatalyzed OligO nucleotide PolymERisation (LOOPER) technology which combines SELEX with modified nucleotides to yield Highly Functionalized Nucleic Acid Polymers (HFNAPs) (Figure 1D). [49,50] Rather than swapping one natural nucleotide for a non-natural nucleotide, limiting the chemical modifications to four, a three-letter codon was used to encode the modifications enabling a wider range of diversity.…”

Section: Biochemical Librariesmentioning

confidence: 99%

DNA‐Encoded Libraries: Towards Harnessing their Full Power with Darwinian Evolution

Dockerill

Winssinger

2022

Angew Chem Int Ed

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DNA‐encoded library (DEL) technologies are transforming the drug discovery process, enabling the identification of ligands at unprecedented speed and scale. DEL makes use of libraries that are orders of magnitude larger than traditional high‐throughput screens. While a DNA tag alludes to a genotype–phenotype connection that is exploitable for molecular evolution, most of the work in the field is performed with libraries where the tag serves as an amplifiable barcode but does not allow “translation” into the synthetic product it is linked to. In this Review, we cover technologies that enable the “translation” of the genetic tag into synthetic molecules, both biochemically and chemically, and explore how it can be used to harness Darwinian evolutionary pressure.

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Section: Biochemical Librariesmentioning

confidence: 99%

DNA‐Encoded Libraries: Towards Harnessing their Full Power with Darwinian Evolution

Dockerill

Winssinger

2022

Angew Chem Int Ed

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“…Methods have since been developed to encode and screen functionalized aptamers. A large range of artificial nucleobases and backbones have been developed enabling the diversification of the standard “four‐letter alphabet” [47, 48] . Hili et al .…”

Section: Dna‐encoded Library Technologiesmentioning

confidence: 99%

DNA‐Encoded Libraries: Towards Harnessing their Full Power with Darwinian Evolution

Dockerill

Winssinger

2022

Angewandte Chemie

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DNA-encoded library (DEL) technologies are transforming the drug discovery process, enabling the identification of ligands at unprecedented speed and scale. DEL makes use of libraries that are orders of magnitude larger than traditional high-throughput screens. While a DNA tag alludes to a genotype-phenotype connection that is exploitable for molecular evolution, most of the work in the field is performed with libraries where the tag serves as an amplifiable barcode but does not allow "translation" into the synthetic product it is linked to. In this Review, we cover technologies that enable the "translation" of the genetic tag into synthetic molecules, both biochemically and chemically, and explore how it can be used to harness Darwinian evolutionary pressure.

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“…[8] The problem of cytosine protonation has been solved using modified PNA nucleobases. [9] Two strategies have been used to design heterocycles mimicking the protonated cytosine. In the first, rearrangement of heteroatoms in pseudoisocytosine [10] (J base, Figure 1) or thio-pseudoisocytosine [11] (L base) places the N-H group in the required position for formation of J(or L) * G-C triplet.…”

Section: Introductionmentioning

confidence: 99%

“…The problem of cytosine protonation has been solved using modified PNA nucleobases [9] . Two strategies have been used to design heterocycles mimicking the protonated cytosine.…”

Section: Introductionmentioning

confidence: 99%

Nucleobase and Linker Modification for Triple‐Helical Recognition of Pyrimidines in RNA Using Peptide Nucleic Acids

et al. 2023

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Triple-helical recognition of any sequence of double-stranded RNA requires high affinity Hoogsteen hydrogen binding to pyrimidine interruptions of polypurine tracts. Because pyrimidines have only one hydrogen bond donor/acceptor on Hoogsteen face, their triple-helical recognition is a formidable problem. The present study explored various five-membered heterocycles and linkers that connect nucleobases to backbone of peptide nucleic acid (PNA) to optimize formation of X * C-G and Y * U-A triplets. Molecular modeling and biophysical (UV melting and isothermal titration calorimetry) results revealed a complex interplay between the heterocyclic nucleobase and linker to PNA backbone. While the five-membered heterocycles did not improve pyrimidine recognition, increasing the linker length by four atoms provided promising gains in binding affinity and selectivity. The results suggest that further optimization of heterocyclic bases with extended linkers to PNA backbone may be a promising approach to triple-helical recognition of RNA.

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Supernatural: Artificial Nucleobases and Backbones to Program Hybridization-Based Assemblies and Circuits

Cited by 8 publications

References 153 publications

DNA‐Encoded Libraries: Towards Harnessing their Full Power with Darwinian Evolution

DNA‐Encoded Libraries: Towards Harnessing their Full Power with Darwinian Evolution

DNA‐Encoded Libraries: Towards Harnessing their Full Power with Darwinian Evolution

Nucleobase and Linker Modification for Triple‐Helical Recognition of Pyrimidines in RNA Using Peptide Nucleic Acids

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