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Metabolites from Marine Macroorganisms of the Red Sea Acting as Promoters or Inhibitors of Amylin Aggregation.
- Source :
-
Biomolecules [Biomolecules] 2024 Aug 06; Vol. 14 (8). Date of Electronic Publication: 2024 Aug 06. - Publication Year :
- 2024
-
Abstract
- Amylin is part of the endocrine pancreatic system that contributes to glycemic control, regulating blood glucose levels. However, human amylin has a high tendency to aggregate, forming isolated amylin deposits that are observed in patients with type 2 diabetes mellitus. In search of new inhibitors of amylin aggregation, we undertook the chemical analyses of five marine macroorganisms encountered in high populations in the Red Sea and selected a panel of 10 metabolites belonging to different chemical classes to evaluate their ability to inhibit the formation of amyloid deposits in the human amylin peptide. The thioflavin T assay was used to examine the kinetics of amyloid aggregation, and atomic force microscopy was employed to conduct a thorough morphological examination of the formed fibrils. The potential ability of these compounds to interact with the backbone of peptides and compete with β-sheet formation was analyzed by quantum calculations, and the interactions with the amylin peptide were computationally examined using molecular docking. Despite their structural similarity, it could be observed that the hydrophobic and hydrogen bond interactions of pyrrolidinones 9 and 10 with the protein sheets result in one case in a stable aggregation, while in the other, they cause distortion from aggregation.
- Subjects :
- Humans
Molecular Docking Simulation
Protein Aggregates drug effects
Aquatic Organisms chemistry
Aquatic Organisms metabolism
Amyloid metabolism
Amyloid chemistry
Amyloid antagonists & inhibitors
Microscopy, Atomic Force
Diabetes Mellitus, Type 2 drug therapy
Diabetes Mellitus, Type 2 metabolism
Hydrophobic and Hydrophilic Interactions
Kinetics
Islet Amyloid Polypeptide chemistry
Islet Amyloid Polypeptide metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2218-273X
- Volume :
- 14
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Biomolecules
- Publication Type :
- Academic Journal
- Accession number :
- 39199339
- Full Text :
- https://doi.org/10.3390/biom14080951