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STUDY OF ZINC BINDING TO NEUROPROTECTIVE PEPTIDES
Abstract
Neurodegenerative diseases such as Alzheimer's and Parkinson's affect an increasing number of people. Their etiology is related to the formation of fibrils and protein aggregates. Therefore, new therapeutic strategies and compounds are required to prevent aggregation of ?-amyloid (A?) peptides. There are some neuropeptides that play an important role in the immune regulation, as well as in neuroprotection; therefore, they might be possible candidates for future drug development. Consequently, our experiments were focused on the synthesis and characterization of novel peptides, derived from NAP (NAPVSIPQ) peptide, which was recognized as a neuroprotective moiety of activity-dependent neuroprotective protein (ADNP) and which protects neurons against A? toxicity. Since NAP peptide protects A? peptides from aggregation, whereas zinc ions are known to induce aggregation, we investigated here the interaction of zinc ions with NAP and two of its analogs. To study the interactions of NAP peptide and its analogs resulted by replacing serine residue in its amino acid sequence by cysteine and histidine with zinc ions, mass spectrometry, FT-IR spectroscopy and atomic force microscopy were applied. The results of our investigations revealed that zinc ions interact and even bind to the three NAP like peptides, suggesting that these small sequences of only eight amino acid residues (NAPVCIPQ and NAPVHIPQ) might be investigated within the aggregation studies of A? peptides. Furthermore, they could be used as potential therapeutic agents in neurodegenerative diseases like amyotrophic lateral sclerosis or Alzheimer?s disease.
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References9
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