Coiled Coil Peptide Tiles (CCPTs): Expanding the Peptide Building Block Design with Multivalent Peptide Macrocycles

Area of Science:

• Biomolecular Engineering
• Materials Science
• Synthetic Biology

Background:

• Peptides are versatile building blocks for biomimetic materials due to their synthetic accessibility and protein-like structures.
• Existing peptide designs offer limited scope for complex material fabrication.

Purpose of the Study:

• To design, synthesize, and characterize novel multivalent peptide macrocycles, termed coiled coil peptide tiles (CCPTs).
• To enable programmable, multidirectional interactions for advanced biomaterials construction.

Main Methods:

• Convergent synthesis using native chemical ligation and Sortase A-mediated cyclization.
• Circular dichroism (CD) for helical stability assessment.
• Size-exclusion chromatography (SEC), HPLC, and fluorescence quenching for complex characterization.
• Molecular dynamics (MD) simulations for structural and dynamic insights.

Main Results:

• Successful synthesis and characterization of CCPTs, revealing enhanced helical stability upon cyclization.
• Demonstrated orthogonal colocalization of CCPT domains with binding partners.
• MD simulations showed CCPT rigidification and expansion upon complexation, providing design guidance.

Conclusions:

• CCPTs represent a novel class of synthetic biomolecular building blocks.
• Cyclization enhances structural stability and enables programmable interactions.
• CCPTs expand the possibilities for coiled coil-based assembly, unlocking new material topologies.