α-Methylation Enables the X-ray Crystallographic Observation of Oligomeric Assemblies Formed by a β-Hairpin Peptide Derived from Aβ.

ABSTRACT: The assembly of the β-amyloid peptide Aβ into toxic oligomers plays a significant role in the neurodegeneration associated with the pathogenesis of Alzheimer's disease. Our laboratory has developed N-methylation as a tool to enable X-ray crystallographic studies of oligomers formed by macrocyclic β-hairpin peptides derived from Aβ. In this investigation, we set out to determine whether α-methylation could be used as an alternative to N-methylation in studying the oligomerization of a β-hairpin peptide derived from Aβ. α-Methylation permits the crystallographic assembly of a triangular trimer and ball-shaped dodecamer, resembling assemblies formed by the N-methylated homolog. Subtle differences are observed in the conformation of the α-methylated peptide when compared t

SUBMITTER: Samdin TD 

PROVIDER: S-EPMC11731301 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature