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Resveratrol interferes with the aggregation of membrane-bound human-IAPP: A molecular dynamics study

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Yksityiskohdat

AlkuperäiskieliEnglanti
Sivut876-881
Sivumäärä6
JulkaisuEuropean Journal of Medicinal Chemistry
Vuosikerta92
DOI - pysyväislinkit
TilaJulkaistu - 6 maaliskuuta 2015
OKM-julkaisutyyppiA1 Alkuperäisartikkeli

Tiivistelmä

Amyloid aggregation of islet amyloid polypeptide (IAPP) in pancreatic tissues is a typical feature of type 2 diabetes mellitus. Resveratrol, a natural product extensively studied for its wide range of biological effects, has been shown to inhibit IAPP aggregation. However, the mechanism by which resveratrol inhibits IAPP aggregation is still far from complete elucidation. Now, an increasing knowledge of the mechanism of amyloid toxicity shifts the target of research towards the development of compounds which can prevent amyloid-mediated membrane damage rather than merely inhibit fiber formation. In this study we used all atom molecular dynamics to investigate the interaction of resveratrol with full-length human IAPP in a negatively charged membrane environment. Our results show that the presence of resveratrol induces the formation of secondary structures (sheets and helices) by inserting in a hydrophobic pocket between the interaction surface of two IAPP molecules in aqueous solution. On the other hand, resveratrol significantly perturbs the interaction of IAPP with negatively charged membranes by anchoring specific hydrophobic regions (23FGA25 and 32VGS34) of the peptide and forming a stable 1:2 IAPP:resveratrol complex at the water/membrane interphase.

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