RT Journal Article
T1 Development of linear β-turn inducers containing peptides as arc mimetics with DNA topological and sequence selectivity
A1 Stefanucci, Azzurra
A1 Santoro, Federica
A1 D’Ingiullo, Sara
A1 Marinaccio, Lorenza
A1 Procino, Eleonora
A1 Learte Aymamí, Soraya
A1 Rodríguez Villar, Jéssica
A1 Mascareñas Cid, José Luis
A1 Amato, Jussara
A1 Arciuolo, Valentina
A1 Randazzo, Antonio
A1 De Rosa, Martina
A1 Brancaccio, Diego
A1 Mollica, Adriano
A1 Carotenuto, Alfonso
K1 Arc mimetic
K1 Peptides
K1 DNA major groove
K1 β-hairpin
AB 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.
PB Elsevier
SN 0223-5234
YR 2025
FD 2025-05
LK https://hdl.handle.net/10347/41167
UL https://hdl.handle.net/10347/41167
LA eng
NO Stefanucci, A., Santoro, F., D’Ingiullo, S., Marinaccio, L., Procino, E., Learte-Aymamí, S., Rodriguez, J., Mascareñas, J. L., Amato, J., Arciuolo, V., Randazzo, A., De Rosa, M., Brancaccio, D., Mollica, A., & Carotenuto, A. (2025). DEVELOPMENT OF LINEAR Β-TURN INDUCERS CONTAINING PEPTIDES AS ARC MIMETICS WITH DNA TOPOLOGICAL AND SEQUENCE SELECTIVITY. European Journal Of Medicinal Chemistry, 289, 117423. https://doi.org/10.1016/j.ejmech.2025.117423
NO A.S. acknowledges financial support under the National Recovery and Resilience Plan (PNRR), Mission 4, Component C2, Investment 1.1, Call for tender No. 1409 published on September 14, 2022 by the Italian Ministry of University and Research (MUR), funded by the European Union-NextGenerationEU-Project Title Ultrasonic Technology for the Sustainable Chemical Synthesis of Peptide-based Therapeutics (US4PepTher)-CUP D53D23016950001-Grant Assignment Decree No. 0001384 adopted on 01-09-2023 by the Italian Ministry of Ministry of University and Research (MUR). A.C. acknowledges PRIN2022 (2022LFFPZE) “PROTAC-based approach to develop broad-spectrum antiviral drugs triggering the proteolysis of the main viral protease”.D.B. acknowledges PRIN2022 (20222HMJLN) “Multi-targeting G-quadruplex ligands as innovative chemotherapeutic agents to combat tumor drug resistance (MuTaG4L)”. J.R. acknowledges grants RYC2022-035154-I (funded by MICIU/AEI/10.13039/501100011033 and by FSE+) and PID2023-146174NA-I00 (funded by MICIU/AEI/10.13039/501100011033 and by FEDER, UE).
DS Minerva
RD 28 abr 2026