Honors Theses

Date of Award

2015

Document Type

Undergraduate Thesis

Department

Biomolecular Sciences

First Advisor

Tracy Brooks

Relational Format

Dissertation/Thesis

Abstract

ADAM-15 is a protein that is up-regulated in many diseases, particularly breast cancer; its over-expression is correlated with more aggressive and invasive phenotypes. The critical core promoter region of ADAM-15 is capable of forming a secondary DNA structure known as a G-quadruplex. The stabilization of this G-quadruplex has the potential to decrease the transcription of the over-expressed ADAM-15 protein. Six hundred forty compounds were screened for their ability to cause a shift in the melting temperature of an ADAM-15 oligonucleotide using FRET melt. Two compounds, NSC 146771 and NSC 260594, produced a significant shift in the melting temperature; further experimentation, such as circular dichroism, cytotoxicity MTS assays, and RT-qPCR, was performed to confirm the ability of these small molecules to stabilize the G-quadruplexes within the ADAM-15 promoter. Neither compound showed cytotoxicity, and NSC 260594 showed an increased capacity for reducing the transcription of ADAM-15. Further pharmacokinetic and pharmacodynamic experimentation needs to be completed, but NSC 260594 shows potential to significantly decrease ADAM-15 expression and therefore improve the prognosis of breast cancer patients.

Accessibility Status

Searchable text

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.