Isolation and characterization of coactivator-binding peptoids from a combinatorial library

Prasanna Alluri, Bo Liu, Peng Yu, Xiangshu Xiao, Thomas Kodadek

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Pharmacologic agents capable of activating the expression of specific genes would be valuable tools in biological research and could potentially be useful therapeutically. Efforts to develop a general solution to this problem have focused on the discovery of cell permeable mimics of native transcription factors comprised of linked DNA-binding and activation domain surrogates. Recently, we reported the isolation of a peptoid, called KBPo2, that binds a fragment of the mammalian coactivator CREB-binding protein (CBP). When delivered to a promoter-bound DNA-binding domain, this peptoid acted as a potent activation domain mimic in human cells. In this paper, we provide full details of the screening experiments and also report further characterization of this molecule as well as the other peptoids that came out of the screen. Of the three peptoids identified as putative CBP ligands, only KBPo2 demonstrated the necessary combination of binding affinity, specificity and cell permeability necessary to function as a potent activation domain mimic in cells. KBPo2 binds to CBP in a region different than that recognized by the native activation peptide from the transcription factor CREB.

Original languageEnglish (US)
Pages (from-to)568-579
Number of pages12
JournalMolecular BioSystems
Volume2
Issue number11
DOIs
StatePublished - Oct 23 2006

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology

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