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- W2787202293 abstract "The self-assembly of insulin to form amyloid fibrils has been widely studied because it is a significant problem in the medical management of diabetes and is an important model system for the investigation of amyloid formation and its inhibition. A few inhibitors of insulin fibrillation have been identified with potencies that could be higher. Knowledge of how these work at the molecular level is not known but important for the development of more potent inhibitors. Here we show that rosmarinic acid completely inhibits amyloid formation by dimeric insulin at pH 2 and 60 °C. In contrast to other polyphenols, rosmarinic acid is soluble in water and does not degrade at elevated temperatures, and thus we were able to decipher the mechanism of inhibition by a combination of solution-state 1H NMR spectroscopy and molecular docking. On the basis of 1H chemical shift perturbations, intermolecular nuclear Overhauser effect enhancements between rosmarinic acid and specific residues of insulin, and slowed dynamics of rosmarinic acid in the presence of insulin, we show that rosmarinic acid binds to a pocket found on the surface of each insulin monomer. This results in the formation of a mixed tetramolecular aromatic network on the surface of insulin dimer, resulting in increased resistance of the amyloidogenic protein to thermal unfolding. This finding opens new avenues for the design of potent inhibitors of amyloid formation and provides strong experimental evidence for the role of surface aromatic clusters in increasing the thermal stability of proteins." @default.
- W2787202293 created "2018-02-23" @default.
- W2787202293 creator A5007792240 @default.
- W2787202293 creator A5058261098 @default.
- W2787202293 date "2018-02-13" @default.
- W2787202293 modified "2023-10-13" @default.
- W2787202293 title "Mechanistic Studies of the Inhibition of Insulin Fibril Formation by Rosmarinic Acid" @default.
- W2787202293 cites W104793819 @default.
- W2787202293 cites W1515676539 @default.
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- W2787202293 cites W1941109177 @default.
- W2787202293 cites W1972459558 @default.
- W2787202293 cites W1979408593 @default.
- W2787202293 cites W1980251868 @default.
- W2787202293 cites W1994307930 @default.
- W2787202293 cites W1995548121 @default.
- W2787202293 cites W1996220552 @default.
- W2787202293 cites W1998205923 @default.
- W2787202293 cites W2001363066 @default.
- W2787202293 cites W2003609792 @default.
- W2787202293 cites W2003719817 @default.
- W2787202293 cites W2010462701 @default.
- W2787202293 cites W2011825508 @default.
- W2787202293 cites W2012721217 @default.
- W2787202293 cites W2017457068 @default.
- W2787202293 cites W2018880174 @default.
- W2787202293 cites W2020305610 @default.
- W2787202293 cites W2023073798 @default.
- W2787202293 cites W2026680843 @default.
- W2787202293 cites W2028864844 @default.
- W2787202293 cites W2034376929 @default.
- W2787202293 cites W2038399240 @default.
- W2787202293 cites W2039735363 @default.
- W2787202293 cites W2040824780 @default.
- W2787202293 cites W2043761562 @default.
- W2787202293 cites W2045262199 @default.
- W2787202293 cites W2045446885 @default.
- W2787202293 cites W2045877329 @default.
- W2787202293 cites W2048631643 @default.
- W2787202293 cites W2048940684 @default.
- W2787202293 cites W2050213438 @default.
- W2787202293 cites W2052999073 @default.
- W2787202293 cites W2053893413 @default.
- W2787202293 cites W2058271282 @default.
- W2787202293 cites W2064212761 @default.
- W2787202293 cites W2068834560 @default.
- W2787202293 cites W2072836683 @default.
- W2787202293 cites W2075981452 @default.
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- W2787202293 cites W2085696583 @default.
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- W2787202293 cites W2088320437 @default.
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- W2787202293 cites W2101614182 @default.
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- W2787202293 cites W2141488428 @default.
- W2787202293 cites W2148892150 @default.
- W2787202293 cites W2159879659 @default.
- W2787202293 cites W2163407325 @default.
- W2787202293 cites W2164818290 @default.
- W2787202293 cites W2246110510 @default.
- W2787202293 cites W2321632516 @default.
- W2787202293 cites W2322540009 @default.
- W2787202293 cites W2327707453 @default.
- W2787202293 cites W2332581925 @default.
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- W2787202293 doi "https://doi.org/10.1021/acs.jpcb.8b00689" @default.
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- W2787202293 hasPublicationYear "2018" @default.
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