DNA-Mediated Peptide Assembly into Protein Mimics.

Area of Science:

• Biochemistry
• Molecular Biology
• Synthetic Biology

Background:

• Designing novel protein structures is complex due to the vast sequence space and intricate protein folding.
• Existing methods face challenges in achieving precise control over the spatial arrangement of multiple peptide units.

Purpose of the Study:

• To develop a novel modular DNA-templated strategy for constructing artificial protein mimics.
• To enable spatial control and efficient assembly of peptide units into stable protein-like structures.

Main Methods:

• Conjugating multiple peptide units to DNA strands.
• Hybridizing DNA-conjugated peptides to a branched DNA trimer template.
• Covalently stapling preorganized peptides to form a single protein mimic unit.

Main Results:

• Efficient construction of a diverse library of protein mimics with varying lengths, sequences, and heptad registers.
• Formation of stable α-helix or coiled-coil motifs in DNA-templated protein mimics, even with weakly interacting peptides.
• Demonstration of dynamic control over secondary and tertiary structures using attached DNA handles.

Conclusions:

• The modular DNA-templated strategy offers a powerful tool for protein mimic design and construction.
• This method facilitates the development of DNA-encoded protein libraries for accelerated discovery of therapeutics, enzymes, and antibody mimics.