Supramolecular Antiparallel β-Sheet Formation by Tetrapeptides Based on Amyloid Sequence

Area of Science:

• Biochemistry
• Structural Biology
• Materials Science

Background:

• Self-assembly of short peptides is a key area of research with diverse applications.
• Truncated peptide fragments from neurodegenerative diseases often adopt beta-sheet structures.
• Aromatic amino acid-rich fragments show a propensity for beta-sheet formation.

Purpose of the Study:

• To report the crystal structure of two aliphatic tetrapeptides, Boc-GAII-OMe and Boc-GGVV-OMe.
• To investigate their self-assembly into beta-sheet structures.
• To compare their properties with native amyloidogenic peptide fragments.

Main Methods:

• X-ray crystallography to determine solid-state structures.
• Analysis of noncovalent interactions, including C-C interactions.
• Ramachandran plot analysis of torsion angles.
• Fourier-transform infrared (FT-IR) spectroscopy.
• Circular dichroism (CD) spectroscopy.
• Congo Red staining and birefringence analysis.

Main Results:

• The crystal structures reveal antiparallel beta-sheet self-assembly stabilized by hydrogen bonding and other noncovalent interactions.
• Peptide 1 exhibits a rare C-C interaction between carbonyl and sp3 carbon atoms.
• Torsion angles confirm beta-sheet conformation.
• FT-IR and CD spectroscopy indicate beta-sheet structures in solid-state and aqueous solution, respectively.
• Congo Red staining shows birefringence, indicating amyloidogenic nature.

Conclusions:

• Short peptides composed solely of aliphatic amino acids can form beta-sheet structures without aromatic residues.
• These aliphatic peptides mimic the self-assembly and amyloidogenic properties of native amyloid fragments.
• The study expands understanding of peptide self-assembly and potential therapeutic targets for neurodegenerative diseases.