Date of Graduation

7-2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Engineering (PhD)

Degree Level

Graduate

Department

Chemical Engineering

Advisor/Mentor

Servoss, Shannon L.

Committee Member

Beitle, Robert R. Jr.

Second Committee Member

Hestekin, Christa N.

Third Committee Member

Thallapuranam, Suresh

Fourth Committee Member

Balachandran, Kartik

Keywords

Pure sciences; Applied sciences; Abeta; Aggregation; Alzeimer's disease; KLVFF; Peptoids

Abstract

Alzheimer’s disease (AD) is the leading form of dementia worldwide. AD patients experience a slow, gradual cognitive decline that includes loss of memory and behavioral stability as the disease progresses. Surprisingly, AD is the sixth leading cause of death in the United States and has had a profound impact on the U.S. economy. Though there are medications to help improve the quality of life of diagnosed patients for a period of time, there is still no cure for AD. AD is characterized by the build-up of amyloid plaques that develop from the aggregation of the amyloid beta protein (Aβ) in the body. Current treatment options for AD has been the development of compounds that can target and either inhibit or modulate the formation of Aβ aggregates.

Several small molecules and peptides have been studied for their ability to interact and inhibit or modulate Aβ aggregation. However, despite promising results in-vitro, none of these compounds have led to a therapeutic treatment. In this study, we demonstrate five novel peptoid modulators of Aβ aggregation. These peptoids were the first to be designed from the hydrophobic core of Aβ. Results have indicated that inclusion of aromatic side chains, peptoid secondary structure, side chain placement, and inclusion of charged sequences have a profound impact on Aβ aggregation. Overall, this study provides insight to the potential of novel peptoids as a therapeutic option for AD.

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