Synthesis, Characterization, and DNA Binding Profile of a Macrocyclic β-Sheet Analogue of ARC Protein.

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.

DOI: 10.1021/acsmedchemlett.5b00363

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Cite this paper

@article{Stefanucci2015SynthesisCA, title={Synthesis, Characterization, and DNA Binding Profile of a Macrocyclic β-Sheet Analogue of ARC Protein.}, author={Azzurra Stefanucci and Jes{\'u}s Mosquera and Eug{\`e}nio V{\'a}zquez and Jos{\'e} L Mascare{\~n}as and Ettore Novellino and Adriano Mollica}, journal={ACS medicinal chemistry letters}, year={2015}, volume={6 12}, pages={1220-4} }