Exploring the central region of amylin and its analogs aggregation: the influence of metal ions and residue substitutions

Mawadda Alghrably; Giulia Bennici; Gabriela Szczupaj; Gabriela Szczupaj; Noura Alasmael; Somayah Qutub; Batoul Maatouk; Kousik Chandra; Michal Nowakowski; Abdul-Hamid Emwas; Mariusz Jaremko

doi:10.3389/fchem.2024.1419019

Frontiers in Chemistry (Jul 2024)

Exploring the central region of amylin and its analogs aggregation: the influence of metal ions and residue substitutions

Mawadda Alghrably,
Giulia Bennici,
Gabriela Szczupaj,
Gabriela Szczupaj,
Noura Alasmael,
Somayah Qutub,
Batoul Maatouk,
Kousik Chandra,
Michal Nowakowski,
Abdul-Hamid Emwas,
Mariusz Jaremko

Affiliations

Mawadda Alghrably: Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
Giulia Bennici: Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
Gabriela Szczupaj: Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
Gabriela Szczupaj: Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Warszawa, Poland
Noura Alasmael: King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
Somayah Qutub: Smart Hybrid Materials Laboratory (SHMs), Chemistry Program, Physical Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
Batoul Maatouk: Smart Hybrid Materials Laboratory (SHMs), Chemistry Program, Physical Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
Kousik Chandra: Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
Michal Nowakowski: Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Warszawa, Poland
Abdul-Hamid Emwas: Core Lab of NMR, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
Mariusz Jaremko: Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia

DOI: https://doi.org/10.3389/fchem.2024.1419019
Journal volume & issue: Vol. 12

Abstract

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Human amylin (hIAPP) is found in the form of amyloid deposits within the pancreatic cells of nearly all patients diagnosed with type 2 diabetes mellitus (T2DM). However, rat amylin (rIAPP) and pramlintide - hIAPP analogs - are both non-toxic and non-amyloidogenic. Their primary sequences exhibit only slight variations in a few amino acid residues, primarily concentrated in the central region, spanning residues 20 to 29. This inspired us to study this fragment and investigate the impact on the aggregation properties of substituting residues within the central region of amylin and its analogs. Six fragments derived from amylin have undergone comprehensive testing against various metal ions by implementing a range of analytical techniques, including Nuclear Magnetic Resonance (NMR) spectroscopy, Thioflavin T (ThT) assays, Atomic Force Microscopy (AFM), and cytotoxicity assays. These methodologies serve to provide a thorough understanding of how the substitutions and interactions with metal ions impact the aggregation behavior of amylin and its analogs.

Published in Frontiers in Chemistry

ISSN: 2296-2646 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Chemistry
Website: http://journal.frontiersin.org/journal/chemistry

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