Title
Rational Design, Synthesis, and Evaluation of Inhibitors for the HIV-1 TAT Interacting Protein Tip60
Date of Award
Spring 4-15-2013
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Biology
First Advisor
Dr. Yujun George Zheng
Second Advisor
Dr. Susanna Fletcher Greer
Third Advisor
Dr. Therese M. Poole
Abstract
The histone acetyltransferase protein, Tip60, has many important functions in epigenetic regulation of gene expression and DNA repair. Our objective is to design, synthesize, and evaluate potent inhibitors for Tip60. Full-length Tip60 (fl-Tip60) and catalytic domain of Tip60 (cat-Tip60) were expressed in E. coli and purified with nickel affinity chromatography. Quantitative analysis of enzyme activities demonstrated that both enzyme forms had very high activity with the substrate H4. To create new Tip60 inhibitors, various histone H3 peptides conjugated with CoA were synthesized using the Fmoc solid-phase peptide synthesis and solution phase synthesis protocols. The results from the inhibition radioactive assay showed that the synthetic H3-CoA conjugates inhibited effectively the enzymatic activity of both fl-Tip60 and cat-Tip60; and the addition of methyl groups to the Lys-4 or Lys-9 residue of H3 aided in a 7-9 fold enhancement in potency in comparison to nascent H3-CoA inhibitor.
DOI
https://doi.org/10.57709/4077152
Recommended Citation
Ngo, Liza D., "Rational Design, Synthesis, and Evaluation of Inhibitors for the HIV-1 TAT Interacting Protein Tip60." Thesis, Georgia State University, 2013.
doi: https://doi.org/10.57709/4077152