Development of linear β-turn inducers containing peptides as arc mimetics with DNA topological and sequence selectivity

In general, biological macromolecules such as proteins interact with the major groove of the ds-DNA via hydrogen bonds formation, thus blocking the site access of TFs to specific DNA sequences. Considering that the primary sequence of arc repressor responsible for DNA binding is well-characterized a...

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Detalles Bibliográficos
Autores: Stefanucci, Azzurra, Santoro, Federica, D’Ingiullo, Sara, Marinaccio, Lorenza, Procino, Eleonora, Learte Aymamí, Soraya, Rodríguez Villar, Jéssica, Mascareñas Cid, José Luis, Amato, Jussara, Arciuolo, Valentina, Randazzo, Antonio, De Rosa, Martina, Brancaccio, Diego, Mollica, Adriano, Carotenuto, Alfonso
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:minerva.usc.gal:10347/41167
Acceso en línea:https://hdl.handle.net/10347/41167
Access Level:acceso abierto
Palabra clave:Arc mimetic
Peptides
DNA major groove
β-hairpin
2306 Química orgánica
Descripción
Sumario:In general, biological macromolecules such as proteins interact with the major groove of the ds-DNA via hydrogen bonds formation, thus blocking the site access of TFs to specific DNA sequences. Considering that the primary sequence of arc repressor responsible for DNA binding is well-characterized as well as the 3D-conformational requisites for its optimal interactions with the specific DNA base-pairs, a series of well-tailored arc analogues could be designed using computational molecular tools and available structural data. These novel molecular entities have been synthesized following ultrasound assisted-solid phase peptide synthesis (US-SPPS), characterized by NMR experiments and screened for TAGA box selectivity on DNA oligomers using a battery of DNA displacement assays. Data obtained show a clear tendency of peptide ACAS_4 to assume a 3-D β-sheet like structure responsible of the interaction with DNA major groove and to bind selectively to the consensus sequence of DNA. For the best of our knowledge this is the first report on a β-sheet arc mimetic endowed with topological and sequence selectivity for the TAGA box of DNA.

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