Synthese van de provincie Antwerpen. (Antwerpen, A.D.L.A., 1960-1961).

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Amyloidogenic peptides for design of inhibitors of peptide aggregation and as templates for new bionanomaterials

Misfolding of proteins from their soluble form into highly insoluble fibrillar deposits can lead to (non-)neurodegenerative disorders or systemic amyloidosis. This class of diseases (for which no therapy is available yet) is called amyloid diseases. Amyloid refers to the extracellular proteinaceous deposits consisting of fibrils. Fibrils are oligomers of misfolded peptides/proteins which are characterized by folding into beta-pleated sheets. A well accepted approach for the interference with beta-sheet formation is the design of soluble beta-sheet mimetics that are able to disrupt the hydrogen bonding network which ultimately leads to the disassembly of fibrils and aggregates. One prominent disease related to the formation of extracellular amyloid is type 2 diabetes. The western aging population shows a dramatic increase in the number of diabetic patients. Type 2 diabetes is characterized by the extracellular deposition of the misfolded human Islet Amyloid PolyPeptide (hIAPP or amylin) in the pancreatic islets of Langerhans and is found in 90% of the diabetic patients. The first part of this thesis describes the development of newly designed soluble beta-sheet breaker peptides based on human amylin. Several approaches towards such beta-sheet breaker peptides were investigated. In chapter 2, the synthesis, spectroscopic analysis and aggregation behaviour, of several backbone-modified amylin(20-29) derivatives is described. Three modified amide bonds at alternate positions were introduced such as ester bonds, N-butylated amides and peptoids using amylin(20-29) as core sequence. In chapter 3, the synthesis of the chiral peptoid building block of L-isoleucine, the solid phase synthesis of the peptoid and retropeptoid sequences of amylin(20-29), and the structural analysis of these amylin derivatives in solution by infrared spectroscopy, circular dichroism and transmission electron microscopy is described. Chapters 4 and 5 deal with the incorporation of a single beta-aminoethane sulfonyl amide moiety or an aminooxy moiety in the highly amyloidogenic peptide sequence amylin(20-29) and its subsequent benzylation featuring the Mitsunobu reaction. Chapter 6 deals with the synthesis of the enantiomer of the L-depsipeptide as was described in chapter 2. In chapter 7, aggregation studies of native amylin(1-37) and derivatives using NMR-spectroscopy are described. The role of histidine 18 in full-length amylin was studied to reveal the initial changes in secondary structure and fibril formation. In chapter 8, design of a covalent triangular shaped molecule with amyloidogenic Abeta(16-22) as a repeating unit and functioning as a cross recognition motif, is described. Identical triangular shaped molecules might be capable to induce spontaneous self-assembly into nanospheres like viral capsids or triangular shaped tubular nanostructures. Chapter 9 describes an alternative approach towards the synthesis of triangular shaped peptide constructs as described in chapter 8. Herein, an efficient and facile synthesis of an N-azido/C-alkynyl Abeta(16-22) derivative is described. Since peptides containing both an azide and an alkyne moiety can be polymerized using the microwave-assisted Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction, this synthetic approach was chosen to obtain cyclic Abeta16-22) oligomers

DEPARTEMENT DE CHIMIE FACULTÉ DES SCIENCES ET DE GÉNIE

à la Faculté des études supérieures de l'Université Laval dans le cadre du programme de maîtrise en chimie pour l'obtention du grade de Maître es science (M. Se.

Destruction de quelques composes polluants phytosanitaires par les composes oxygenes actives par des complexes metalliques

Available from INIST (FR), Document Supply Service, under shelf-number : RP 185 (4016) / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEMinistere de l'Environnement, 75 - Paris (France). Service de la Recherche et des Affaires Economiques (SRAE)FRFranc

Entwicklung eines Verfahrens zur modellbasierten Ueberpruefung von digitalen Systemen

Available from TIB Hannover: RR 8753(96-2) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman