β-Turn Mimicking Crosslinking Provides Hyperstability and Fast Folding Kinetics for Short Collagen Triple Helices

Area of Science:

• Biochemistry
• Structural Biology
• Peptide Chemistry

Background:

• Stabilizing collagen triple helix mimics, particularly heterotrimers, is synthetically challenging.
• Existing crosslinking methods face limitations like structural perturbations and sequence constraints.

Purpose of the Study:

• To develop a novel strategy for creating stable, miniaturized collagen triple helix mimics.
• To overcome limitations associated with interstrand sidechain crosslinking methods.

Main Methods:

• Incorporation of terminal β-turn-mimicking linkers at both ends of collagen peptides.
• Design and synthesis of double-turn-containing peptide mimics.
• Kinetic analysis of intramolecular triple helix formation.

Main Results:

• Demonstrated compatibility of β-turn linkers with collagen triple helix hydrogen bonding geometry.
• Achieved highly stable, intramolecular triple helical structures in miniaturized mimics.
• Observed significantly accelerated folding kinetics for intramolecular triple helix formation.

Conclusions:

• Terminal linker installation provides a viable strategy for stable collagen triple helix mimic design.
• Miniaturized triple helix mimics exhibit enhanced folding properties.
• Kinetic studies offer novel mechanistic insights into collagen folding at varying temperatures.