Copper(II) and Amylin Analogues: A Complicated Relationship.

Mawadda Alghrably, Dorota Dudek, Abdul-Hamid M. Emwas, Lukasz Jaremko, Mariusz Jaremko, Magdalena Rowińska-Żyrek

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Protein aggregation has attracted substantial interest because of its role in causing many serious illnesses, such as neurodegenerative diseases and type II diabetes. Recent studies have shown that protein aggregation can be prevented by forming metal ion complexes with a target protein, which affects their conformation in solution and their physical properties, such as aggregation. Thus, understanding the interactions between aggregating molecules and bioactive metal ions such as Cu2+ is beneficial for new drug discovery. Pramlintide, a synthetic peptide drug, and its natural counterpart rat amylin are known to be resistant to aggregation because of the presence of proline residues, which are usually β-sheet "breakers" within their amino acid sequence. Here, we investigate the Cu2+ coordination properties of pramlintide and rat amylin using nuclear magnetic resonance, circular dichroism, electron paramagnetic resonance, ultraviolet-visible spectroscopy, potentiometry, and mass spectrometry. We test the influence of Cu2+ on the aggregation properties of these amylin analogues with thioflavin T assays. We find that both peptides form stable complexes with Cu2+ with similar affinities at a 1:1 ratio. The N-termini of both peptides are involved in Cu2+ binding; His18 imidazole is an equally attractive binding site in the case of pramlintide. Our results show that Cu2+ ions influence the aggregation of pramlintide, but not that of rat amylin.
Original languageEnglish (US)
Pages (from-to)2527-2535
Number of pages9
JournalInorganic chemistry
Issue number4
StatePublished - Feb 7 2020

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: Financial support by the National Science Centre (UMO2017/26/A/ST5/00364, to M. R.-Ż.) is gratefully acknowledged. M.J., M.A., A.H.E., and Ł. J. would like to thank the King Abdullah University of Science and Technology (KAUST) for the financial support.


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