The NAP peptide (H2N-1NAPVSIPQ8-CONH2) is a truncated version of the activity-dependent neuroprotective protein. Its neuroprotective activities consist of the inhibition of Aβ(25–35) and Aβ(1–40) fibrillogenesis as well as protection against Aβ-induced neurotoxicity and prevention of microtubule disruption associated with Alzheimer's disease. Therefore, we synthesized NAP and its mutant peptide with the sequence H2N-1NAPVCIPQ8-COOH (NAPCOH) by replacing serine S5 with cysteine C5. Both native and mutant peptides were further used to study their interaction with iron ions. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry, Fourier transform infrared spectroscopy and also atomic force microscopy were used to probe Fe3+ binding to both peptides. Contrary to the expected results, the investigated peptides underwent different oxidation processes, with resultant reduced Fe2+ ions. These ions, and not the original Fe3+ ions, were found to bind to each of the non-oxidized peptides.
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