Synthesis of Different Analogs of Ab(9-16) Peptide Mass spectrometric evidence for heavy metal binding

Amyloid-b (Ab) peptides are proteins associated with Alzheimer s disease (AD), because the extracellular Ab deposits are the main cause of this disorder. The aggregation of Ab has been shown to depend on the interactions with metal ions, such as copper, zinc, aluminum or iron. The N-terminal sequence of Ab(1-42) or Ab(1-40) peptides, namely Ab(1-16) peptide fragment, is considered the metal binding site involved in AD neurodegeneration and amyloidogenesis. Therefore, we have investigated different peptide sequences to understand the role played by some amino acid residues in metal binding. In this paper, we report the chemical synthesis of Ab(9-16) peptide and its analogs by Fmoc/tBu strategy and the mass spectrometric evidence for metal ion binding to newly synthesized peptides. MALDI-ToF mass spectrometry proved to be a reliable tool to detect and identify the metal ion complexes of all peptides investigated with copper, iron and zinc ions.