Synthesis, Characterization, and DNA Binding Profile of a Macrocyclic ?-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 ?-sheet ARC repressor mimetic, based on the amino acid sequence of the ?-sheet domain in the ARC protein. The ability of this ?-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 ?-sheets folded peptides as valuable substitutes of transcription factor proteins in drug therapy.

SUBMITTER: Stefanucci A 

PROVIDER: S-EPMC4677364 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature