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A library-derived peptide inhibitor of the BZLF1 transcription factor.

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Brennan, Andrew 


Transcription factor dysregulation is associated with many diseases, including cancer. Peptide-based molecules are increasingly recognised as important modulators of difficult intracellular protein-protein interaction targets, with peptide library screening consequently proven to be a viable strategy in developing inhibitors against a wide range of transcription factors (TFs). However, current strategies simply select the highest affinity of binding to a target TF rather than the ability to inhibit TF function. Here, we utilise our Transcription Block Survival (TBS) screening platform to enable high-throughput identification of peptides that inhibit TFs from binding to cognate DNA sites, hence inhibiting functionality. In this study, we explore whether the TBS can be expanded to derive a potent and functional peptide inhibitor of the BZLF1 transcription factor. The library-derived peptide, AcidicW, is shown to form a more stable dimer with BZLF1 than the BZLF1 homodimer, with a thermal denaturation temperature exceeding 80°C. AcidicW can also functionally inhibit the BZLF1:TRE DNA interaction with high potency and an IC50 of 612 nM.


Publication status: Published

Funder: University of Bath; doi:


BZLF1, PCA, ZEBRA, peptide antagonists, peptide screening, transcription factor, Transcription Factors, DNA-Binding Proteins, Trans-Activators, Viral Proteins, Herpesvirus 4, Human, Peptides, DNA

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J Pept Sci

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Cancer Research UK (A26941)
Medical Research Council (MR/T028254/1)
Biotechnology and Biological Sciences Research Council (BB/R017956/1)