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dc.contributor.advisorRaleigh, Daniel Pen_US
dc.contributor.authorMarek, Peter Jamesen_US
dc.contributor.otherDepartment of Chemistryen_US
dc.date.accessioned2013-05-22T17:35:13Z
dc.date.available2013-05-22T17:35:13Z
dc.date.issued1-May-12en_US
dc.date.submitted12-Mayen_US
dc.identifierMarek_grad.sunysb_0771E_10899en_US
dc.identifier.urihttp://hdl.handle.net/1951/59782
dc.description205 pg.en_US
dc.description.abstractAmyloid deposition has been implicated to play a role in the pathology of over 40 human diseases including Alzheimer's, Parkinson's, type 2 diabetes and systemic amyloidosis, to name a few. All amyloid fibrils are characterized by a cross &beta-pleated sheet structure with interstrand hydrogen bonds running parallel to the long axis of the fibril. Islet amyloid polypeptide (IAPP) is a 37-residue peptide hormone that is the major proteinaceous component of pancreatic islet amyloid deposition that develops during type 2 diabetes. These deposits have been shown to play a role in the decrease of islet mass and &beta-cell apoptosis, which are typical pathologies developed during type 2 diabetes. The aggregation process of how IAPP goes from an unstructured monomer to an ordered peptide aggregate with significant &beta-sheet secondary structure is highly complex and involves a number of transient species that are highly dynamic and metastable. This research provides insights into the biophysical mechanisms and environmental components that can enhance amyloid assembly by IAPP using chemical, biophysical and kinetic methods. My work included the development of a new method to synthesize IAPP via microwave solid-phase peptide synthesis; the examination of the role of aromatic amino acids in IAPP via a triple mutant in which the three aromatic amino acids were substituted with leucines; probing the nature lag phase species populated during amyloid formation via the unnatural fluorescent amino acid, p-cyanophenylalanine; and the study of the effects of ionic strength and ion composition on amyloid formation by IAPP. These studies aim to provide a better understanding of the intrinsic factors inherent to IAPP, as well as extrinsic environmental factors, that can decrease the stability of monomeric IAPP and induce amyloid formation.en_US
dc.description.sponsorshipStony Brook University Libraries. SBU Graduate School in Department of Chemistry. Charles Taber (Dean of Graduate School).en_US
dc.formatElectronic Resourceen_US
dc.language.isoen_USen_US
dc.publisherThe Graduate School, Stony Brook University: Stony Brook, NY.en_US
dc.subject.lcshChemistry--Biophysicsen_US
dc.subject.otherAmyloid, Islet Amyloid Polypeptideen_US
dc.titleBiophysical Insights into Amyloid Formation by Islet Amyloid Polypeptideen_US
dc.typeDissertationen_US
dc.description.advisorAdvisor(s): Raleigh, Daniel P. Committee Member(s): Tonge, Peter J; Carrico, Isaac ; Baum, Jean.en_US
dc.mimetypeApplication/PDFen_US


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