title: 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.
authors.affiliation: Dipartimento di Chimica, Sapienza, Università di Roma , P.le A. Moro 5, 00187 Rome, Italy.
authors.forename: Azzurra
authors.initials: A
authors.lastname: Stefanucci
authors.affiliation: Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Departamento de Química Orgánica, Universidade de Santiago de Compostela , 15782 Santiago de Compostela, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Mosquera
authors.affiliation: Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Departamento de Química Orgánica, Universidade de Santiago de Compostela , 15782 Santiago de Compostela, Spain.
authors.forename: Eugènio
authors.initials: E
authors.lastname: Vázquez
authors.affiliation: Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Departamento de Química Orgánica, Universidade de Santiago de Compostela , 15782 Santiago de Compostela, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Mascareñas
authors.affiliation: Dipartimento di Farmacia, Università di Napoli "Federico II" , Via D. Montesano, 49, 80131 Naples, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.affiliation: Dipartimento di Farmacia, Università di Chieti-Pescara "G. d'Annunzio" , Via dei Vestini 31, 66100 Chieti, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Mollica
keywords: ARC repressor; DNA recognition; major groove; solid phase peptide synthesis; transcription factors; β-sheet macrocycles