Date Approved

2026

Degree Type

Open Access Senior Honors Thesis

Department or School

Chemistry

First Advisor

Deborah Heyl-Clegg, Ph.D.

Second Advisor

Hedeel Guy-Evans, Ph.D.

Third Advisor

Harriet Lindsay, Ph.D.

Abstract

Both cancer and Alzheimer’s disease (AD) affect many people in the United States and impact the families of patients suffering from these challenging illnesses. Recently, it has been reported that these two diseases share several key pathophysiological features, and an inverse relationship exists between them. These diseases share several biochemical modulators, most notably the amyloid-beta protein, which affects tissues in both AD and cancer by misfolding and aggregating. Phosphorylation is believed to regulate the aggregation and toxicity of amyloid-beta by altering the protein's shape and charge, thereby changing its interactions with cells. Phosphorylation can also toggle some proteins on and off, a common regulatory mechanism in the body. This study focuses on the first 16 amino acids of the amyloid-beta peptide sequence, as well as the 1-28 fragment, which has previously been shown to exhibit some anticancer activity. Serine is the phosphorylation point located at positions 8 and 26, so this is where we made a change to this peptide strand. Substituting this amino acid with aspartate is assumed to mimic permanent phosphorylation due to its similar size, shape, and negative charge. A similar effect happens with glutamate. However, changing to alanine has an opposite effect, causing constant deactivation. By replacing the serine with different amino acids and comparing the resulting fragments with the parent fragment, this study determines whether constant “activation” through phosphorylation of this protein can influence the inhibition of lung cancer cells. All peptides were made by solid-phase peptide synthesis, purified by high-performance liquid chromatography, and evaluated using an MTT assay. The IC50 values of all peptide fragments were calculated and compared to determine their relative anticancer activity.

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