Cargando…

Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG(2)T(G(3)T)(3)] and Its Derivatives with an Abasic Site Replacing Single Thymidine

In this paper, we report our investigations on five T30175 analogues, prepared by replacing sequence thymidines with abasic sites (S) one at a time, in comparison to their natural counterpart in order to evaluate their antiproliferative potential and the involvement of the residues not belonging to...

Descripción completa

Detalles Bibliográficos
Autores principales: Virgilio, Antonella, Benigno, Daniela, Pecoraro, Annalisa, Russo, Annapina, Russo, Giulia, Esposito, Veronica, Galeone, Aldo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268168/
https://www.ncbi.nlm.nih.gov/pubmed/34208896
http://dx.doi.org/10.3390/ijms22137040
_version_ 1783720298954096640
author Virgilio, Antonella
Benigno, Daniela
Pecoraro, Annalisa
Russo, Annapina
Russo, Giulia
Esposito, Veronica
Galeone, Aldo
author_facet Virgilio, Antonella
Benigno, Daniela
Pecoraro, Annalisa
Russo, Annapina
Russo, Giulia
Esposito, Veronica
Galeone, Aldo
author_sort Virgilio, Antonella
collection PubMed
description In this paper, we report our investigations on five T30175 analogues, prepared by replacing sequence thymidines with abasic sites (S) one at a time, in comparison to their natural counterpart in order to evaluate their antiproliferative potential and the involvement of the residues not belonging to the central core of stacked guanosines in biological activity. The collected NMR (Nuclear Magnetic Resonance), CD (Circular Dichroism), and PAGE (Polyacrylamide Gel Electrophoresis) data strongly suggest that all of them adopt G-quadruplex (G4) structures strictly similar to that of the parent aptamer with the ability to fold into a dimeric structure composed of two identical G-quadruplexes, each characterized by parallel strands, three all-anti-G-tetrads and four one-thymidine loops (one bulge and three propeller loops). Furthermore, their antiproliferative (MTT assay) and anti-motility (wound healing assay) properties against lung and colorectal cancer cells were tested. Although all of the oligodeoxynucleotides (ODNs) investigated here exhibited anti-proliferative activity, the unmodified T30175 aptamer showed the greatest effect on cell growth, suggesting that both its characteristic folding in dimeric form and its presence in the sequence of all thymidines are crucial elements for antiproliferative activity. This straightforward approach is suitable for understanding the critical requirements of the G-quadruplex structures that affect antiproliferative potential and suggests its application as a starting point to facilitate the reasonable development of G-quadruplexes with improved anticancer properties.
format Online
Article
Text
id pubmed-8268168
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-82681682021-07-10 Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG(2)T(G(3)T)(3)] and Its Derivatives with an Abasic Site Replacing Single Thymidine Virgilio, Antonella Benigno, Daniela Pecoraro, Annalisa Russo, Annapina Russo, Giulia Esposito, Veronica Galeone, Aldo Int J Mol Sci Article In this paper, we report our investigations on five T30175 analogues, prepared by replacing sequence thymidines with abasic sites (S) one at a time, in comparison to their natural counterpart in order to evaluate their antiproliferative potential and the involvement of the residues not belonging to the central core of stacked guanosines in biological activity. The collected NMR (Nuclear Magnetic Resonance), CD (Circular Dichroism), and PAGE (Polyacrylamide Gel Electrophoresis) data strongly suggest that all of them adopt G-quadruplex (G4) structures strictly similar to that of the parent aptamer with the ability to fold into a dimeric structure composed of two identical G-quadruplexes, each characterized by parallel strands, three all-anti-G-tetrads and four one-thymidine loops (one bulge and three propeller loops). Furthermore, their antiproliferative (MTT assay) and anti-motility (wound healing assay) properties against lung and colorectal cancer cells were tested. Although all of the oligodeoxynucleotides (ODNs) investigated here exhibited anti-proliferative activity, the unmodified T30175 aptamer showed the greatest effect on cell growth, suggesting that both its characteristic folding in dimeric form and its presence in the sequence of all thymidines are crucial elements for antiproliferative activity. This straightforward approach is suitable for understanding the critical requirements of the G-quadruplex structures that affect antiproliferative potential and suggests its application as a starting point to facilitate the reasonable development of G-quadruplexes with improved anticancer properties. MDPI 2021-06-30 /pmc/articles/PMC8268168/ /pubmed/34208896 http://dx.doi.org/10.3390/ijms22137040 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Virgilio, Antonella
Benigno, Daniela
Pecoraro, Annalisa
Russo, Annapina
Russo, Giulia
Esposito, Veronica
Galeone, Aldo
Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG(2)T(G(3)T)(3)] and Its Derivatives with an Abasic Site Replacing Single Thymidine
title Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG(2)T(G(3)T)(3)] and Its Derivatives with an Abasic Site Replacing Single Thymidine
title_full Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG(2)T(G(3)T)(3)] and Its Derivatives with an Abasic Site Replacing Single Thymidine
title_fullStr Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG(2)T(G(3)T)(3)] and Its Derivatives with an Abasic Site Replacing Single Thymidine
title_full_unstemmed Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG(2)T(G(3)T)(3)] and Its Derivatives with an Abasic Site Replacing Single Thymidine
title_short Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG(2)T(G(3)T)(3)] and Its Derivatives with an Abasic Site Replacing Single Thymidine
title_sort exploring new potential anticancer activities of the g-quadruplexes formed by [(gtg(2)t(g(3)t)(3)] and its derivatives with an abasic site replacing single thymidine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268168/
https://www.ncbi.nlm.nih.gov/pubmed/34208896
http://dx.doi.org/10.3390/ijms22137040
work_keys_str_mv AT virgilioantonella exploringnewpotentialanticanceractivitiesofthegquadruplexesformedbygtg2tg3t3anditsderivativeswithanabasicsitereplacingsinglethymidine
AT benignodaniela exploringnewpotentialanticanceractivitiesofthegquadruplexesformedbygtg2tg3t3anditsderivativeswithanabasicsitereplacingsinglethymidine
AT pecoraroannalisa exploringnewpotentialanticanceractivitiesofthegquadruplexesformedbygtg2tg3t3anditsderivativeswithanabasicsitereplacingsinglethymidine
AT russoannapina exploringnewpotentialanticanceractivitiesofthegquadruplexesformedbygtg2tg3t3anditsderivativeswithanabasicsitereplacingsinglethymidine
AT russogiulia exploringnewpotentialanticanceractivitiesofthegquadruplexesformedbygtg2tg3t3anditsderivativeswithanabasicsitereplacingsinglethymidine
AT espositoveronica exploringnewpotentialanticanceractivitiesofthegquadruplexesformedbygtg2tg3t3anditsderivativeswithanabasicsitereplacingsinglethymidine
AT galeonealdo exploringnewpotentialanticanceractivitiesofthegquadruplexesformedbygtg2tg3t3anditsderivativeswithanabasicsitereplacingsinglethymidine