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Synergistic DNA‐ and Protein‐Based Recognition Promote an RNA‐Templated Bio‐orthogonal Reaction

Biomolecular assemblies composed of proteins and oligonucleotides play a central role in biological processes. While in nature, oligonucleotides and proteins usually assemble via non‐covalent interactions, synthetic conjugates have been developed which covalently link both modalities. The resulting...

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Autores principales: McLoughlin, Niall M., Kuepper, Arne, Neubacher, Saskia, Grossmann, Tom N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362040/
https://www.ncbi.nlm.nih.gov/pubmed/33914384
http://dx.doi.org/10.1002/chem.202101103
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author McLoughlin, Niall M.
Kuepper, Arne
Neubacher, Saskia
Grossmann, Tom N.
author_facet McLoughlin, Niall M.
Kuepper, Arne
Neubacher, Saskia
Grossmann, Tom N.
author_sort McLoughlin, Niall M.
collection PubMed
description Biomolecular assemblies composed of proteins and oligonucleotides play a central role in biological processes. While in nature, oligonucleotides and proteins usually assemble via non‐covalent interactions, synthetic conjugates have been developed which covalently link both modalities. The resulting peptide‐oligonucleotide conjugates have facilitated novel biological applications as well as the design of functional supramolecular systems and materials. However, despite the importance of concerted protein/oligonucleotide recognition in nature, conjugation approaches have barely utilized the synergistic recognition abilities of such complexes. Herein, the structure‐based design of peptide‐DNA conjugates that bind RNA through Watson‐Crick base pairing combined with peptide‐mediated major groove recognition is reported. Two distinct conjugate families with tunable binding characteristics have been designed to adjacently bind a particular RNA sequence. In the resulting ternary complex, their peptide elements are located in proximity, a feature that was used to enable an RNA‐templated click reaction. The introduced structure‐based design approach opens the door to novel functional biomolecular assemblies.
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spelling pubmed-83620402021-08-17 Synergistic DNA‐ and Protein‐Based Recognition Promote an RNA‐Templated Bio‐orthogonal Reaction McLoughlin, Niall M. Kuepper, Arne Neubacher, Saskia Grossmann, Tom N. Chemistry Full Papers Biomolecular assemblies composed of proteins and oligonucleotides play a central role in biological processes. While in nature, oligonucleotides and proteins usually assemble via non‐covalent interactions, synthetic conjugates have been developed which covalently link both modalities. The resulting peptide‐oligonucleotide conjugates have facilitated novel biological applications as well as the design of functional supramolecular systems and materials. However, despite the importance of concerted protein/oligonucleotide recognition in nature, conjugation approaches have barely utilized the synergistic recognition abilities of such complexes. Herein, the structure‐based design of peptide‐DNA conjugates that bind RNA through Watson‐Crick base pairing combined with peptide‐mediated major groove recognition is reported. Two distinct conjugate families with tunable binding characteristics have been designed to adjacently bind a particular RNA sequence. In the resulting ternary complex, their peptide elements are located in proximity, a feature that was used to enable an RNA‐templated click reaction. The introduced structure‐based design approach opens the door to novel functional biomolecular assemblies. John Wiley and Sons Inc. 2021-06-01 2021-07-16 /pmc/articles/PMC8362040/ /pubmed/33914384 http://dx.doi.org/10.1002/chem.202101103 Text en © 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Full Papers
McLoughlin, Niall M.
Kuepper, Arne
Neubacher, Saskia
Grossmann, Tom N.
Synergistic DNA‐ and Protein‐Based Recognition Promote an RNA‐Templated Bio‐orthogonal Reaction
title Synergistic DNA‐ and Protein‐Based Recognition Promote an RNA‐Templated Bio‐orthogonal Reaction
title_full Synergistic DNA‐ and Protein‐Based Recognition Promote an RNA‐Templated Bio‐orthogonal Reaction
title_fullStr Synergistic DNA‐ and Protein‐Based Recognition Promote an RNA‐Templated Bio‐orthogonal Reaction
title_full_unstemmed Synergistic DNA‐ and Protein‐Based Recognition Promote an RNA‐Templated Bio‐orthogonal Reaction
title_short Synergistic DNA‐ and Protein‐Based Recognition Promote an RNA‐Templated Bio‐orthogonal Reaction
title_sort synergistic dna‐ and protein‐based recognition promote an rna‐templated bio‐orthogonal reaction
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362040/
https://www.ncbi.nlm.nih.gov/pubmed/33914384
http://dx.doi.org/10.1002/chem.202101103
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