A library-derived peptide inhibitor of the BZLF1 transcription factor.
BZLF1
PCA
ZEBRA
peptide antagonists
peptide screening
transcription factor
Journal
Journal of peptide science : an official publication of the European Peptide Society
ISSN: 1099-1387
Titre abrégé: J Pept Sci
Pays: England
ID NLM: 9506309
Informations de publication
Date de publication:
02 Dec 2023
02 Dec 2023
Historique:
revised:
12
11
2023
received:
19
04
2023
accepted:
13
11
2023
medline:
2
12
2023
pubmed:
2
12
2023
entrez:
2
12
2023
Statut:
aheadofprint
Résumé
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 IC
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3557Subventions
Organisme : Cancer Research UK
ID : A26941
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T028254/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R017956/1
Pays : United Kingdom
Informations de copyright
© 2023 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.
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