Synergistic DNA- and Protein-Based Recognition Promote an RNA-Templated Bio-orthogonal Reaction |
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Authors: | Niall M McLoughlin Dr Arne Kuepper Dr Saskia Neubacher Prof?Dr Tom N Grossmann |
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Institution: | 1. Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit Amsterdam, Amsterdam, 1081 HZ The Netherlands;2. Chemical Genomics Centre of the Max Planck Society, Dortmund, 44227 Germany |
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Abstract: | 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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Keywords: | bio-conjugation peptides RNA recognition self-assembly strain-promoted click reaction |
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