title: Amylin Amyloid Inhibition by Flavonoid Baicalein: Key Roles of Its Vicinal Dihydroxyl Groups of the Catechol Moiety.
abstract: Amyloid formation of the 37-residue amylin is involved in the pathogenesis of type 2 diabetes and, potentially, diabetes-induced neurological deficits. Numerous flavonoids exhibit inhibitory effects against amylin amyloidosis, but the mechanisms of inhibition remain unclear. Screening a library of natural compounds uncovered a potent lead compound, the flavone baicalein. Baicalein inhibits amylin amyloid formation and reduces amylin-induced cytotoxicity. Analogue analyses demonstrated, for the first time, key roles of the vicinal hydroxyl groups on the A-ring. We provided mass spectrometric evidence that incubating baicalein and amylin leads to their conjugation, consistent with a Schiff base mechanism.
authors.affiliation: Department of Biochemistry, ‡Center for Drug Discovery, and §Translational Obesity Research Center, Virginia Polytechnic Institute & State University , Blacksburg, Virginia 24061, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Velander
authors.affiliation: Department of Biochemistry, ‡Center for Drug Discovery, and §Translational Obesity Research Center, Virginia Polytechnic Institute & State University , Blacksburg, Virginia 24061, United States.
authors.forename: Ling
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Biochemistry, ‡Center for Drug Discovery, and §Translational Obesity Research Center, Virginia Polytechnic Institute & State University , Blacksburg, Virginia 24061, United States.
authors.forename: W Keith
authors.initials: WK
authors.lastname: Ray
authors.affiliation: Department of Biochemistry, ‡Center for Drug Discovery, and §Translational Obesity Research Center, Virginia Polytechnic Institute & State University , Blacksburg, Virginia 24061, United States.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Helm
authors.affiliation: Department of Biochemistry, ‡Center for Drug Discovery, and §Translational Obesity Research Center, Virginia Polytechnic Institute & State University , Blacksburg, Virginia 24061, United States.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D004353:Drug Evaluation, Preclinical; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000648:ultrastructure; D013058:Mass Spectrometry; D046529:Microscopy, Electron, Transmission; D013329:Structure-Activity Relationship
chemical_list: D044950:Flavanones; D006727:Hormone Antagonists; D058228:Islet Amyloid Polypeptide; C006680:baicalein