Structural Insights on Tiny Peptide Nucleic Acid (PNA) Analogues of miRNA-34a: An in silico and Experimental Integrated Approach(25 views visite) Moccia M, Mercurio FA, Langella E, Piacenti V, Leone M, Adamo MFA, Saviano M
Front Chem (ISSN: 2296-2646linking), 2020 Nov 23; 8: 568575-568575.
Keywords Parole chiave: Nmr, Pna, Mirna-34a, Molecular Dynamics, Tumor Suppressor
Affiliations Affiliazioni: *** IBB - CNR ***
Institute of Crystallography, National Research Council, Department of Chemical Sciences and Materials Technologies, Bari, Italy.
Institute of Biostructures and Bioimaging, National Research Council, Naples, Italy.
Royal College of Surgeons in Ireland, Department of Pharmaceutical and Medicinal Chemistry, Dublin, Ireland.
References Riferimenti: Not available. Non disponibili.
Structural Insights on Tiny Peptide Nucleic Acid (PNA) Analogues of miRNA-34a: An in silico and Experimental Integrated Approach
In the present work, structural features of the interaction between peptide nucleic acid (PNA)-based analogs of the tumor-suppressor microRNA-34a with both its binding sites on MYCN mRNA were investigated. In particular, the region from base 1 to 8 ("seed" region) of miR-34a was reproduced in the form of an 8-mer PNA fragment (tiny PNA), and binding to target 3'UTR MYCN mRNA, was studied by a seldom reported and detailed NMR characterization, providing evidence for the formation of anti-parallel duplexes with a well-organized structural core. The formation of PNA-3'UTR duplexes was also confirmed by Circular Dichroism, and their melting curves were measured by UV spectroscopy. Nevertheless, this study offered a valuable comparison between molecular dynamics predictions and experimental evidence, which showed great correlation. Preliminary uptake assays were carried out in Neuroblastoma Kelly cells, using short peptide conjugates as carriers and FITC fluorescent tag for subcellular localization. Moderate internalization was observed without the use of transfecting agents. The reported results corroborate the interest toward the design and development of chimeric PNA/RNA sequences as effective RNA-targeting agents.
Structural Insights on Tiny Peptide Nucleic Acid (PNA) Analogues of miRNA-34a: An in silico and Experimental Integrated Approach
202 Records (197 escludendo Abstract e Conferenze). Impact factor totale: 783.486 (761.403 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 821.396 (799.16 escludendo Abstract e Conferenze).
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