Histidine-Lacked Aβ(1–16) Peptides: pH-Dependent Conformational Changes in Metal Ion Binding

• Published in: International journal of peptide research and therapeutics Vol. 26; no. 4; pp. 2529 - 2546
• Main Authors: Habasescu, Laura, Jureschi, Monica, Petre, Brindusa-Alina, Mihai, Marcela, Gradinaru, Robert-Vasile, Murariu, Manuela, Drochioiu, Gabi
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.12.2020; Springer Nature B.V
• Subjects: Alanine; Alzheimer's disease; Amyloid; Animal Anatomy; Atomic force microscopy; Biochemistry; Biomedical and Life Sciences; Circular dichroism; Conformation; Heavy metals; High-performance liquid chromatography; Histidine; Histology; Ions; Life Sciences; Mass spectroscopy; Metal ions; Molecular Medicine; Morphology; Neurodegenerative diseases; Nickel; Peptide synthesis; Peptides; pH effects; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Polymer Sciences; Serine; Ser-Aβ(1–16); Alzheimer’s disease; Metal binding; Amyloid-β peptides; Ala-Aβ(1–16); Mass spectrometry; Circular dichroism
• ISSN: 1573-3149; 1573-3904
• DOI: 10.1007/s10989-020-10048-0

The region 1–16 of the amyloid-β peptides associated with Alzheimer’s disease can be considered as the metal-binding domain, and the residues His 6 , His 13 , and His 14 have been identified as ligands that coordinate heavy metal ions. To establish the role played by the three histidine residues of the Aβ(1–16) sequence in binding metal ions, two variants of Aβ(1–16) peptide fragment (H- 1 DAEFR H DSGYEV HH QK 16 -NH 2 ) were synthesized by Fmoc/ t Bu Solid Phase Peptide Synthesis strategy and purified by RP-HPLC. The three histidine residues were replaced by either three serine residues to form Ser-Aβ(1–16): H- 1 DAEFR S DSGYEV SS QK 16 -NH 2 or three alanine ones to form Ala–Aβ(1–16): H- 1 DAEFR A DSGYEV AA QK 16 -NH 2 . The three peptides were comparatively characterized by mass spectrometry (MS), circular dichroism spectroscopy (CD) and atomic force microscopy (AFM), being subsequently used to study their interaction with metal ions at various pH values. During our experiments, significant pH-dependent changes in the conformation of these peptides have been observed and reported. AFM images showed dramatic changes in the film morphology of peptides upon binding metal ions. In the MS spectra we have unambiguously identified several metal–peptide molecular ions, thus confirming the affinity of Aβ(1–16) peptides to copper and nickel ions. The newly synthesized peptides may bring new evidence on the relationship of histidine residues in amyloid-β peptides with metal ions. In addition, new directions for research and experimental works are suggested.