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

February 24, 2022

Title

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

Author

Alessandro Marchetti, Dr. Andrea Pizzi, Dr. Greta Bergamaschi, Dr. Nicola Demitri, Dr. Ulrike Stollberg, Prof. Ulf Diederichsen, Dr. Claudia Pigliacelli, Prof. Pierangelo Metrangolo

Year

2022

Journal

Chemistry A European Journal

Abstract

Iodination has long been employed as a successful labelling strategy to gain structural insights into proteins and other biomolecules via several techniques, including Small Angle X-ray Scattering, Inductively Coupled Plasma Mass Spectrometer (ICP-MS), and single-crystal crystallography. However, when dealing with smaller biomolecular systems, interactions driven by iodine may significantly alter their self-assembly behaviour. The engineering of amyloidogenic peptides for the development of ordered nanomaterials has greatly benefitted from this possibility. Still, to date, iodination has exclusively been applied to aromatic residues. In this work, an aliphatic bis-iodinated amino acid was synthesized and included into a custom pentapeptide, which showed enhanced fibrillogenic behaviour. Peptide single crystal X-ray structure and powder X-ray diffraction on its dried water solution demonstrated the key role of iodine atoms in promoting intermolecular interactions that drive the peptide self-assembly into amyloid fibrils. These findings enlarge the library of halogenated moieties available for directing and engineering the self-assembly of amyloidogenic peptides.

Instrument

V-630

Keywords

biomolecules, amyloidogenic peptides,