AI Article Synopsis
- Designing new protein structures is tough due to the complexity of protein folding and the huge variety of sequences.
- The researchers developed a DNA-templated method to create protein-like structures by using DNA to organize and bind peptide units together.
- This approach allows for the creation of a diverse library of protein mimics with unique properties and can be used to dynamically control their shapes, paving the way for new medical advances.
Article Abstract
The design of new protein structures is challenging due to their vast sequence space and the complexity of protein folding. Here, we report a new modular DNA-templated strategy to construct protein mimics. We achieve the spatial control of multiple peptide units by conjugation with DNA and hybridization to a branched DNA trimer template followed by covalent stapling of the preorganized peptides into a single unit. A library of protein mimics with different lengths, sequences, and heptad registers has been efficiently constructed. DNA-templated protein mimics show an α-helix or coiled-coil motif formation even when they are constructed from weakly interacting peptide units. Their attached DNA handles can be used to exert dynamic control over the protein mimics' secondary and tertiary structures. This modular strategy will facilitate the development of DNA-encoded protein libraries for the rapid discovery of new therapeutics, enzymes, and antibody mimics.
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| http://dx.doi.org/10.1021/jacs.3c08984 | DOI Listing |
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