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

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• 作者：Azzurra Stefanucci ; Jes煤s Mosquera ; Eug猫nio V谩zquez ; Jos茅 L. Mascare帽as ; Ettore Novellino ; Adriano Mollica
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2015
• 出版时间：December 10, 2015
• 年：2015
• 卷：6
• 期：12
• 页码：1220-1224
• 全文大小：404K
• ISSN：1948-5875

文摘

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 尾-sheet ARC repressor mimetic, based on the amino acid sequence of the 尾-sheet domain in the ARC protein. The ability of this 尾-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 尾-sheets folded peptides as valuable substitutes of transcription factor proteins in drug therapy.