Document Type and Release Option
Thesis (open access)
Dr. Amanda Stewart White
Transcription factors are important proteins that regulate gene expression and protein synthesis. Transcription factors can either boost the gene’s transcription rate by helping RNA polymerase activate transcription or restrict it by interfering with RNA polymerase, thereby repressing transcription. Nuclear factor-kappa-B (NF-κB) transcription factors are a family of proteins that control the synthesis of proteins involved in many cellular processes such as inflammatory and immune responses, cell growth, and apoptosis. However, the overexpression and activation of these transcription factors is linked to deadly conditions such as cancer and neurodegenerative diseases which currently have few safe cures. The goal of this research is to design and synthesize peptides to mimic the size, shape, structure and function of NF-κB. This will allow peptides to compete with and inhibit NF-κB from binding DNA, thus preventing the overexpression of proteins. To explore such possibilities, one peptide was analyzed. The binding affinity for between the peptide and κB DNA was determined using Isothermal Titration Calorimetry (ITC). The secondary structure of the peptide was determined using circular dichroism (CD). Initial data will direct the synthesis of new peptides that will show improved DNA binding affinity and will be screened for inhibition studies. A review of other β-sheet peptides is included to provide more context of their importance in supporting life and how they bind to DNA.
Markowich, Nicholas A., "Designing Peptides to Bind kappa B DNA and Mimic NF-kappa B Protein Complexes" (2020). University Honors Program Theses. 515.