28 February 2022
Centro Congressi Partenope
Europe/Rome timezone

Triplex-Peptide Nucleic Acid (PNA) biological systems investigated through advanced computational methods

28 Feb 2022, 17:15
Aula Magna (Centro Congressi Partenope)

Aula Magna

Centro Congressi Partenope

Via Partenope, 36 - Napoli


Mr. Antonio Lupia (Department of Pharmacy, University Federico II of Naples)


Peptide Nucleic Acids (PNAs), introduced by Nielsen et al. in 1991, are synthetic DNA/RNA analogues and represent a promising tool for gene modulation in anticancer treatment[1]. In the PNA structure, repetitive N-2-aminoethyl-glycine units replace the traditional sugar-phosphate DNA backbone, and the polyamide chain is connected to nucleobase covalently via carboxymethyl spacer. Thanks to their uncharged peptidyl backbone and resistance towards chemical and enzymatic degradation, PNAs can form hybrid complexes with complementary DNA or RNA strands [2-3]. In this view, advanced computational methods based on both conventional and accelerated Molecular Dynamics (cMD and aMD, respectively) simulations were helpful to accurately elucidate the atomistic structural organisation of two differently protonated PNAs structures wrapped into triplex DNA/PNA. In particular, aMD allowed us to improve the conformational space sampling by reducing energy barriers separating different states of a system, thus observing atomistic details about the conformational changes of the two triplex systems. In fact, although the mechanistic aspects for the formation of PNA-DNA triplexes are known, detailed structural information on the PNA-DNA heterotriplexes are still missing. Our findings are in agreement with experimental data and lay the foundation for a further development of novel PNAs in anticancer therapy.

[1] Nielsen, P.E., Egholm, M., Berg, R.H., Buchardt, O., 1991. Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science 254, 1497–1500.

[2] Verona, M. D. et al. Focus on PNA Flexibility and RNA Binding using Molecular Dynamics and Metadynamics. Sci. Rep. 7, 42799;

[3] Zarrilli, F.; Amato, F.; Morgillo, C.M.; Pinto, B.; Santarpia, G.; Borbone, N.; D’Errico, S.; Catalanotti, B.; Piccialli, G.; Castaldo, G.; Oliviero, G. Peptide Nucleic Acids as miRNA Target Protectors for the Treatment of Cystic Fibrosis. Molecules 2017, 22, 1144.

Department Department of Pharmacy

Primary authors

Mr. Antonio Lupia (Department of Pharmacy, University Federico II of Naples) Federica Moraca (Department of Pharmacy, University "Federico II" of Naples) BRUNO CATALANOTTI (Università degli Studi di Napoli Federico II) Dr. Carmine Marco Morgillo (Department of Pharmacy, University of Naples Federico II)

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