Synthesis, characterization, and DNA binding profile of a macrocyclic β-Sheet analogue of ARC protein

Azzurra Stefanucci, Jesús Mosquera, Eugènio Vázquez, José L. Mascareñas, Ettore Novellino, Adriano Mollica

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

ARC repressor (apoptosis repressor with caspase recruitment domain) is a protein which binds selectively to a specific sequence of DNA. In humans, ARC is primarily expressed in striated muscle tissue, which normally does not undergo rapid cell turnover. This suggests that ARC may play a protective role in the prevention against Duchenne Muscular Dystrophy and several types of tumors. In this Letter we report the synthesis, characterization, and conformational analysis of a β-sheet ARC repressor mimetic, based on the amino acid sequence of the β-sheet domain in the ARC protein. The ability of this β-sheet macrocycle to bind to double-stranded DNA was also evaluated using spectroscopic methods. Our data show that the synthetic peptide has a defined conformation and is able to bind DNA with reasonable affinity. These initial results lay the groundwork for the design of novel β-sheets folded peptides as valuable substitutes of transcription factor proteins in drug therapy.

Original languageEnglish
Pages (from-to)1220-1224
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume6
Issue number12
DOIs
Publication statusPublished - 10 Dec 2015

Keywords

  • ARC repressor
  • DNA recognition
  • major groove
  • solid phase peptide synthesis
  • transcription factors
  • β-sheet macrocycles

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