期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 27, 期 40, 页码 10477-10483出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202101103
关键词
bio-conjugation; peptides; RNA recognition; selfassembly; strain-promoted click reaction
资金
- European Research Council (ERC) [678623]
- AstraZeneca
- Bayer CropScience
- Bayer HealthCare
- Boehringer Ingelheim
- Merck KGaA
- Max Planck Society
- European Research Council (ERC) [678623] Funding Source: European Research Council (ERC)
Peptide-DNA conjugates designed for binding with RNA through Watson-Crick base pairing combined with peptide-mediated major groove recognition represent a structure-based approach to novel biomolecular assemblies. By designing two distinct conjugate families with tunable binding characteristics for adjacent binding to a specific RNA sequence, a ternary complex is formed. The proximity of peptide elements in the complex enables an RNA-templated click reaction, introducing a new approach for functional biomolecular assemblies.
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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