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Studies toward the design, synthesis, and evaluation of new therapeutic and diagnostic agents for amyloid- associated diseases

Abstract

Amyloid-misfolding is a characteristic of many different disorders. This thesis is separated into the focus of pathogenic amyloid entities evident in Alzheimer's disease and pre-eclampsia. Alzheimer's disease (AD) is a neurodegenerative disorder that attributes its toxicity to the presence of amyloid-[Beta] aggregates. These aggregates have been documented to confer its toxicity by interfering with the functions of cellular proteins. To reduce toxicity, one of the strategies in the development of an AD therapeutic includes the design of a small molecule that can prevent the interaction of amyloid aggregates with cellular proteins. Current amyloid-binding molecules (BTA molecules) have restricted potential as an AD therapeutic because of their low solubility in aqueous media. To increase the utility of these BTA derivatives, the hydrophilicity of these molecules must be increased. Chapter 2 of this thesis is focused on addressing this solubility issue with the synthesis of a BTA derivative that is decorated with zwitterionic oligomers. Pre- eclampsia is gestational disorder that has been recently characterized with the presence of amyloid aggregates. This disorder harms the mother and her unborn baby. Despite the alarms that this disorder raises, effective diagnostic measures are limited primarily by the heterogeneous manifestation of clinical symptoms exhibited by patients with pre-eclampsia. The second part of this thesis focuses on a different facet of amyloid misfolding diseases to develop diagnostic tools for pre-eclampsia

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