Fibril Structure Demonstrates the Role of Iodine Labelling on a Pentapeptide Self-Assembly

Area of Science:

• Biomolecular engineering
• Materials science
• Chemical synthesis

Background:

• Iodination is a common labeling strategy for biomolecules using techniques like X-ray scattering and mass spectrometry.
• Iodine interactions can influence the self-assembly of smaller biomolecular systems, including amyloidogenic peptides.
• Current iodination methods primarily target aromatic residues in peptides.

Purpose of the Study:

• To synthesize a novel aliphatic iodinated amino acid.
• To incorporate this amino acid into a pentapeptide to investigate its effect on fibrillogenesis.
• To explore new strategies for directing the self-assembly of amyloidogenic peptides.

Main Methods:

• Synthesis of an aliphatic bis-iodinated amino acid.
• Incorporation of the modified amino acid into a custom pentapeptide.
• Characterization using peptide single crystal X-ray structure and powder X-ray diffraction.

Main Results:

• The synthesized pentapeptide exhibited enhanced fibrillogenic behavior.
• X-ray crystallography revealed the crucial role of iodine atoms in promoting intermolecular interactions.
• Powder X-ray diffraction confirmed the self-assembly into amyloid fibrils driven by these interactions.

Conclusions:

• Aliphatic iodination can effectively direct the self-assembly of peptides into amyloid fibrils.
• This work introduces a new class of halogenated building blocks for peptide self-assembly.
• Findings expand the toolkit for engineering ordered nanomaterials from amyloidogenic peptides.