Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG<sub>2</sub>T(G<sub>3</sub>T)<sub>3</sub>] 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...
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/7040 |
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| author | Antonella Virgilio Daniela Benigno Annalisa Pecoraro Annapina Russo Giulia Russo Veronica Esposito Aldo Galeone |
| author_facet | Antonella Virgilio Daniela Benigno Annalisa Pecoraro Annapina Russo Giulia Russo Veronica Esposito Aldo Galeone |
| author_sort | Antonella Virgilio |
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| 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-<i>anti-</i>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. |
| first_indexed | 2024-03-09T04:44:11Z |
| format | Article |
| id | doaj.art-a5008e52504a4ffe91988b1da59231ce |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:44:11Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a5008e52504a4ffe91988b1da59231ce2023-12-03T13:17:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213704010.3390/ijms22137040Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG<sub>2</sub>T(G<sub>3</sub>T)<sub>3</sub>] and Its Derivatives with an Abasic Site Replacing Single ThymidineAntonella Virgilio0Daniela Benigno1Annalisa Pecoraro2Annapina Russo3Giulia Russo4Veronica Esposito5Aldo Galeone6Department of Pharmacy, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Napoli, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Napoli, ItalyIn 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-<i>anti-</i>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.https://www.mdpi.com/1422-0067/22/13/7040G-quadruplexabasic siteaptamersantiproliferative activity |
| spellingShingle | Antonella Virgilio Daniela Benigno Annalisa Pecoraro Annapina Russo Giulia Russo Veronica Esposito Aldo Galeone Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG<sub>2</sub>T(G<sub>3</sub>T)<sub>3</sub>] and Its Derivatives with an Abasic Site Replacing Single Thymidine International Journal of Molecular Sciences G-quadruplex abasic site aptamers antiproliferative activity |
| title | Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG<sub>2</sub>T(G<sub>3</sub>T)<sub>3</sub>] and Its Derivatives with an Abasic Site Replacing Single Thymidine |
| title_full | Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG<sub>2</sub>T(G<sub>3</sub>T)<sub>3</sub>] and Its Derivatives with an Abasic Site Replacing Single Thymidine |
| title_fullStr | Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG<sub>2</sub>T(G<sub>3</sub>T)<sub>3</sub>] 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<sub>2</sub>T(G<sub>3</sub>T)<sub>3</sub>] and Its Derivatives with an Abasic Site Replacing Single Thymidine |
| title_short | Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG<sub>2</sub>T(G<sub>3</sub>T)<sub>3</sub>] and Its Derivatives with an Abasic Site Replacing Single Thymidine |
| title_sort | exploring new potential anticancer activities of the g quadruplexes formed by gtg sub 2 sub t g sub 3 sub t sub 3 sub and its derivatives with an abasic site replacing single thymidine |
| topic | G-quadruplex abasic site aptamers antiproliferative activity |
| url | https://www.mdpi.com/1422-0067/22/13/7040 |
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