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To mimic the metal binding sites of the human IAPP (h\u2010IAPP), a soluble, single\u2010point mutated variant of r\u2010IAPP, having a histidine residue in place of Arg18, was synthesized, that is, r\u2010IAPP(1\u201337; R18H). The peptide IAPP(1\u20138) was also characterized to have deeper insight into the N\u2010terminus copper(II)\u2010binding features of r\u2010IAPP as well as of its mutated form. A combined experimental (thermodynamic and spectroscopic) and computational approach allowed us to assess the metal loading and the coordination features of the whole IAPP. At physiological pH, the N\u2010terminal amino group is the Cu<jats:sup>2+<\/jats:sup> main binding site both of entire r\u2010IAPP and of its mutated form that mimics h\u2010IAPP. The histidine residue present in this mutated polypeptide accounts for the second Cu<jats:sup>2+<\/jats:sup> binding. We can speculate that the copper driven toxicity of h\u2010IAPP in comparison to that of r\u2010IAPP can be attributed to the different metal loading and the presence of a second metal anchoring site, the His<jats:sub>18<\/jats:sub>, whose role is usually invoked in the process of h\u2010IAPP aggregation.<\/jats:p>","DOI":"10.1002\/chem.201704910","type":"journal-article","created":{"date-parts":[[2017,11,7]],"date-time":"2017-11-07T07:52:39Z","timestamp":1510041159000},"page":"17898-17902","source":"Crossref","is-referenced-by-count":12,"title":["From Peptide Fragments to Whole Protein: Copper(II) Load and Coordination Features of IAPP"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1556-934X","authenticated-orcid":false,"given":"Antonio","family":"Magr\u00ec","sequence":"first","affiliation":[{"name":"Istituto di Biostrutture e Bioimmagini-CNR  Via P. 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