Objective:

To develop a modular protein–foldamer pair for assembling hybrid nanostructures with controlled geometry.

Approach:

• Development of Protein-Foldamer Pair: Researchers at Ludwig-Maximilians-Universität München created a protein–foldamer pair designed to act as a modular molecular connector, using ribosome display to identify a suitable protein partner.
• Binding Affinity Assessment: Biolayer interferometry was employed to demonstrate that the identified protein variant C10 binds the foldamer with nanomolar affinity.
• Structural Analysis: Nuclear magnetic resonance spectroscopy and X-ray crystallography were used to elucidate the binding interactions between the foldamer and the C10 scaffold.
• Assembly Characterization: Mass spectrometry and ion mobility measurements were utilized to analyze larger assemblies formed from the foldamer and protein components.

Key Findings:

• The C10 protein variant binds selectively to the right-handed P-helix of the foldamer with high affinity.
• The binding interface features a large contact surface with stable interactions, enabling modular assembly.
• The researchers demonstrated the ability to vary the spacing and orientation of proteins by altering foldamer length and geometry.
• The resulting structures included cyclic assemblies and a one-dimensional zigzag network with porous characteristics.

Limitations:

• The work represents a proof-of-principle rather than a fully developed material.
• Further research is needed to explore the practical applications of these structures.