DNA- and RNA-binding ability of oligoDapT, a nucleobase-decorated peptide, for biomedical applications

Domenica Musumeci,1,2 Valentina Roviello,3 Giovanni N Roviello1 1CNR-Institute of Biostructure and Bioimaging, Naples, Italy; 2Department of Chemical Sciences, University of Naples Federico II, Naples, Italy; 3Analytical Chemistry for the Environment and Centro Servizi Metereologici Avanzati, Unive...

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Autores principales:	Musumeci D, Roviello V, Roviello GN
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	nucleopeptides nucleic acid-interaction poly rA-binding circular dichroism Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/939641a3a84c4d64a8c6cdb80a87d991
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spelling	oai:doaj.org-article:939641a3a84c4d64a8c6cdb80a87d9912021-12-02T08:49:58ZDNA- and RNA-binding ability of oligoDapT, a nucleobase-decorated peptide, for biomedical applications1178-2013https://doaj.org/article/939641a3a84c4d64a8c6cdb80a87d9912018-05-01T00:00:00Zhttps://www.dovepress.com/dna--and-rna-binding-ability-of-oligodapt-a-nucleobase-decorated-pepti-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Domenica Musumeci,1,2 Valentina Roviello,3 Giovanni N Roviello1 1CNR-Institute of Biostructure and Bioimaging, Naples, Italy; 2Department of Chemical Sciences, University of Naples Federico II, Naples, Italy; 3Analytical Chemistry for the Environment and Centro Servizi Metereologici Avanzati, University of Naples Federico II, Naples, Italy Background: Nucleobase-bearing peptides and their interaction with DNA and RNA are an important topic in the development of therapeutic approaches. On one hand, they are highly effective for modulating the nucleic-acid-based biological processes. On the other hand, they permit to overcome some of the main factors limiting the therapeutic efficacy of natural oligonucleotides, such as their rapid degradation by nucleases. Methods and results: This article describes the synthesis and characterization of a novel thymine-bearing nucleoamino acid based on the l-diaminopropionic acid (l-Dap) and its solid phase oligomerization to α-peptides (oligoDapT), characterized using mass spectrometry, spectroscopic techniques, and scanning electron microscopy (SEM) analysis. The interaction of the obtained nucleopeptide with DNA and RNA model systems as both single strands (dA12, rA12, and poly(rA)) and duplex structures (dA12/dT12 and poly(rA)/poly(rU)) was investigated by means of circular dichroism (CD) and ultraviolet (UV) experiments. From the analysis of our data, a clear ability of the nucleopeptide to bind nucleic acids emerged, with oligoDapT being able to form stable complexes with both unpaired and double-stranded DNA and RNA. In particular, dramatic changes in the dA12/dT12 and poly(rA)/poly(rU) structures were observed as a consequence of the nucleopeptide binding. CD titrations revealed that multiple peptide units bound all the examined nucleic acid targets, with TLdap/A or TLdap/A:T(U) ratios >4 in case of oligoDapT/DNA and ~2 in oligoDapT/RNA complexes. Conclusion: Our findings seem to indicate that Dap-based nucleopeptides are interesting nucleic acid binding-tools to be further explored with the aim to efficiently modulate DNA- and RNA-based biological processes. Keywords: nucleopeptides, nucleic acid interaction, poly(rA) binding, circular dichroismMusumeci DRoviello VRoviello GNDove Medical Pressarticlenucleopeptidesnucleic acid-interactionpoly rA-bindingcircular dichroismMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 2613-2629 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	nucleopeptides nucleic acid-interaction poly rA-binding circular dichroism Medicine (General) R5-920
spellingShingle	nucleopeptides nucleic acid-interaction poly rA-binding circular dichroism Medicine (General) R5-920 Musumeci D Roviello V Roviello GN DNA- and RNA-binding ability of oligoDapT, a nucleobase-decorated peptide, for biomedical applications
description	Domenica Musumeci,1,2 Valentina Roviello,3 Giovanni N Roviello1 1CNR-Institute of Biostructure and Bioimaging, Naples, Italy; 2Department of Chemical Sciences, University of Naples Federico II, Naples, Italy; 3Analytical Chemistry for the Environment and Centro Servizi Metereologici Avanzati, University of Naples Federico II, Naples, Italy Background: Nucleobase-bearing peptides and their interaction with DNA and RNA are an important topic in the development of therapeutic approaches. On one hand, they are highly effective for modulating the nucleic-acid-based biological processes. On the other hand, they permit to overcome some of the main factors limiting the therapeutic efficacy of natural oligonucleotides, such as their rapid degradation by nucleases. Methods and results: This article describes the synthesis and characterization of a novel thymine-bearing nucleoamino acid based on the l-diaminopropionic acid (l-Dap) and its solid phase oligomerization to α-peptides (oligoDapT), characterized using mass spectrometry, spectroscopic techniques, and scanning electron microscopy (SEM) analysis. The interaction of the obtained nucleopeptide with DNA and RNA model systems as both single strands (dA12, rA12, and poly(rA)) and duplex structures (dA12/dT12 and poly(rA)/poly(rU)) was investigated by means of circular dichroism (CD) and ultraviolet (UV) experiments. From the analysis of our data, a clear ability of the nucleopeptide to bind nucleic acids emerged, with oligoDapT being able to form stable complexes with both unpaired and double-stranded DNA and RNA. In particular, dramatic changes in the dA12/dT12 and poly(rA)/poly(rU) structures were observed as a consequence of the nucleopeptide binding. CD titrations revealed that multiple peptide units bound all the examined nucleic acid targets, with TLdap/A or TLdap/A:T(U) ratios >4 in case of oligoDapT/DNA and ~2 in oligoDapT/RNA complexes. Conclusion: Our findings seem to indicate that Dap-based nucleopeptides are interesting nucleic acid binding-tools to be further explored with the aim to efficiently modulate DNA- and RNA-based biological processes. Keywords: nucleopeptides, nucleic acid interaction, poly(rA) binding, circular dichroism
format	article
author	Musumeci D Roviello V Roviello GN
author_facet	Musumeci D Roviello V Roviello GN
author_sort	Musumeci D
title	DNA- and RNA-binding ability of oligoDapT, a nucleobase-decorated peptide, for biomedical applications
title_short	DNA- and RNA-binding ability of oligoDapT, a nucleobase-decorated peptide, for biomedical applications
title_full	DNA- and RNA-binding ability of oligoDapT, a nucleobase-decorated peptide, for biomedical applications
title_fullStr	DNA- and RNA-binding ability of oligoDapT, a nucleobase-decorated peptide, for biomedical applications
title_full_unstemmed	DNA- and RNA-binding ability of oligoDapT, a nucleobase-decorated peptide, for biomedical applications
title_sort	dna- and rna-binding ability of oligodapt, a nucleobase-decorated peptide, for biomedical applications
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/939641a3a84c4d64a8c6cdb80a87d991
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DNA- and RNA-binding ability of oligoDapT, a nucleobase-decorated peptide, for biomedical applications

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