FTIR and MS Evidence for Heavy Metal Binding to Anti-amyloidal NAP-Like Peptides

The octapeptide NAP (NAPVSIPQ) is a small sequence from the activity-dependent neuroprotective protein (ADNP), which is able to provide neuroprotection against Aβ toxicity even at low concentration. NAP provides protection against oxidative stress to brain cells and stimulates neurite outgrowth providing a neurotrophic and neuroprotective function. Therefore, we have investigated copper and silver binding to two NAP-like peptides, since our previous research revealed unexpected iron binding to such peptides. Here, we report on Cu(I) and Ag(I) binding to NAP and its Cys 5 mutant. Our results revealed that NAP bind up to two silver ions but only one of copper as shown by Fourier transform infrared (FTIR) spectroscopy and MALDI-ToF mass spectrometry (MS). Surprisingly, its Cys 5 mutant can bind four silver ions or three of copper, despite the fact that it is a small peptide molecule. The results were discussed in the view of NAP protection against Aβ induced neurotoxicity associated with Alzheimer disease (AD) and the relationship between Aβ peptides and heavy metal ions.