Nuclear Factor Kappa B is one of the many transcription factors that assist in regulating gene expression for a variety of genes. Due to various factors, there can be overexpression of certain genes which can lead to deleterious effects. The aim of this project is to design and synthesize a series of peptide mimics that can bind with the kappa B DNA sites and help decrease the overexpression of these genes by competing with and displacing the natural transcription factor NF-KB. In order to prepare peptides which can successfully bind the NF-KB DNA sites, peptides will be beta sheets which mimic the structure of NF-KB. Peptides will be varied in length, specifically focusing on the length of the loop region where DNA binding occurs in the native protein. The amino acid sequence will also be modified to include hydrogen bonding side chains and aromatic residues which have been shown to be crucial for binding by NF-KB. Circular dichroism (CD) will be completed to determine the secondary structures of all peptides, and the DNA binding affinities will be determined for each peptide by isothermal titration calorimetry (ITC) or by fluorescence spectroscopy. Once all initial studies are completed, the peptide with the optimal structural features and the highest binding affinity will be further studied to evaluate its ability to compete with the natural NF-KB. Results of these studies will be presented.

NF-KB peptide mimics' role in regulation of gene expression

ACS Spring 2022

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