Dalton Transactions Blog

The formation of peptide or protein aggregates is a common feature of many different forms of neurodegenerative disorders including Alzheimer’s disease, Parkinson’s disease and prion diseases. It is also widely accepted that various metal ions can play a significant role in the conformational changes of these peptides/proteins.

In this HOT article, Kállay and co-workers report on the synthesis and study of the copper complexes of rIAPP fragments. First of all the terminally protected tridecapeptide rIAPP(17–29) was investigated in which the potentially metal binding amino acid residues are located in the N-terminus. The surprisingly high affinity of this peptide towards complexation with copper(II) promoted a systematic study on the shorter fragments including rIAPP(17–22) (Ac-VRSSNN-NH₂), rIAPP(17–20) (Ac-VRSS-NH₂), its mutant peptides (Ac-VASSNH₂ and Ac-VRAA-NH₂) and rIAPP(19–22) (Ac-SSNN-NH₂). The peptides can be classified into two different categories: (i) the tetrapeptides Ac-VRSS-NH₂, Ac-VASS-NH₂ and Ac-VRAA-NH₂ can interact with copper(II) only under strongly alkaline conditions (pH > 10.0) and the formation of only one species with four amide nitrogen coordination can be detected; (ii) the peptides Ac-VRSSNNLGPVLPP-NH₂, Ac-VRSSNN-NH₂ and Ac-SSNN-NH₂ can form complexes above pH 6.0 with the major stoichiometries [CuH₋₂L], [CuH₋₃L]⁻ and [CuH₋₄L]²⁻. The data supports the idea that  rIAPP(17–29) can interact with copper(II) ions under physiological conditions and the SSNN tetrapeptide fragment can be considered as the shortest sequence responsible for metal binding.

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Copper(II) complexes of rat amylin fragments
Csilla Kállay, Ágnes Dávid, Sarolta Timári, Eszter Márta Nagy, Daniele Sanna, Eugenio Garribba, Giovanni Micera, Paolo De Bona, Giuseppe Pappalardo, Enrico Rizzarelli and Imre Sóvágó
Dalton Trans., 2011, Advance Article
DOI: 10.1039/C1DT10835B