A blend of two resveratrol derivatives abolishes hIAPP amyloid growth and membrane damage(412 views)(PDF public131 views) Sciacca MFM, Chillemi R, Sciuto S, Greco V, Messineo C, Kotler SA, Lee DK, Brender JR, Ramamoorthy A, La Rosa C, Milardi D
Bba-Gen Subjects (ISSN: 0005-2736print, 0005-2736linking), 2018 Mar 17; N/D: 1793-1902.
Istituto CNR di Biostrutture e Bioimmagini- Sede Secondaria di Catania, Via Paolo Gaifami 18, 95126 Catania, Italy., Universita degli Studi di Catania, Dipartimento di Scienze Chimiche, Viale Andrea Doria 6, 95125 Catania, Italy., Biophysics and Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA., Department of Fine Chemistry, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea., Universita degli Studi di Catania, Dipartimento di Scienze Chimiche, Viale Andrea Doria 6, 95125 Catania, Italy. Electronic address: clarosa@unict.it., Istituto CNR di Biostrutture e Bioimmagini- Sede Secondaria di Catania, Via Paolo Gaifami 18, 95126 Catania, Italy. Electronic address: dmilardi@unict.it.,
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A blend of two resveratrol derivatives abolishes hIAPP amyloid growth and membrane damage
Type II diabetes mellitus (T2DM) is characterized by the presence of amyloid deposits of the human islet amyloid polypeptide (hIAPP) in pancreatic beta-cells. A wealth of data supports the hypothesis that hIAPP's toxicity is related to an abnormal interaction of amyloids with islet cell membranes. Thus, many studies aimed at finding effective therapies for T2DM focus on the design of molecules that are able to inhibit hIAPP's amyloid growth and the related membrane damage as well. Based on this view and inspired by its known anti-amyloid properties, we have functionalized resveratrol with a phosphoryl moiety (4'-O-PR) that improves its solubility and pharmacological properties. A second resveratrol derivative has also been obtained by conjugating resveratrol with a dimyristoylphosphatidyl moiety (4'-DMPR). The use of both compounds resulted in abolishing both amyloid growth and amyloid mediated POPC/POPS membrane damage in tube tests. We propose that a mixture of a water-soluble anti-aggregating compound and its lipid-anchored derivative may be employed as a general strategy to prevent and/or to halt amyloid-related membrane damage.
A blend of two resveratrol derivatives abolishes hIAPP amyloid growth and membrane damage