{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T18:56:04Z","timestamp":1781117764198,"version":"3.54.1"},"reference-count":32,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Center for Gene \u2018Therapy and Drugs based on RNA Technology\u2019","award":["CN00000041"],"award-info":[{"award-number":["CN00000041"]}]},{"name":"National Center for Gene \u2018Therapy and Drugs based on RNA Technology\u2019","award":["E63C22000940007"],"award-info":[{"award-number":["E63C22000940007"]}]},{"name":"European Union-NextGenerationEU and financed by PNRR MUR-M4C2-Investimento 1.4-CUP UNINA","award":["CN00000041"],"award-info":[{"award-number":["CN00000041"]}]},{"name":"European Union-NextGenerationEU and financed by PNRR MUR-M4C2-Investimento 1.4-CUP UNINA","award":["E63C22000940007"],"award-info":[{"award-number":["E63C22000940007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this paper, we study the biological properties of two TBA analogs containing one and two extra G-tetrads, namely TBAG3 and TBAG4, respectively, and two further derivatives in which one of the small loops at the bottom (TBAG41S) or the large loop at the top (TBAG4GS) of the TBAG4 structure has been completely modified by replacing all loop residues with abasic site mimics. The therapeutical development of the TBA was hindered by its low thermodynamic and nuclease stability, while its potential as an anticancer\/antiproliferative molecule is also affected by the anticoagulant activity, being a side effect in this case. In order to obtain suitable TBA analogs and to explore the involvement of specific aptamer regions in biological activity, the antiproliferative capability against DU 145 and MDAMB 231 cancer cell lines (MTT), the anticoagulant properties (PT), the biological degradability (nuclease stability assay) and nucleolin (NCL) binding ability (SPR) of the above described TBA derivatives have been tested. Interestingly, none of the TBA analogs exhibits an anticoagulant activity, while all of them show antiproliferative properties to the same extent. Furthermore, TBAG4 displays extraordinary nuclease stability and promising antiproliferative properties against breast cancer cells binding NCL efficiently. These results expand the range of G4-structures targeting NCL and the possibility of developing novel anticancer and antiviral drugs.<\/jats:p>","DOI":"10.3390\/ijms232314921","type":"journal-article","created":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T02:53:29Z","timestamp":1669690409000},"page":"14921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Properties and Potential Antiproliferative Activity of Thrombin-Binding Aptamer (TBA) Derivatives with One or Two Additional G-Tetrads"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5371-1813","authenticated-orcid":false,"given":"Daniela","family":"Benigno","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, I-80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0873-5250","authenticated-orcid":false,"given":"Antonella","family":"Virgilio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, I-80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6103-8748","authenticated-orcid":false,"given":"Ivana","family":"Bello","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, I-80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7762-0708","authenticated-orcid":false,"given":"Sara","family":"La Manna","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, I-80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5674-9112","authenticated-orcid":false,"given":"Valentina","family":"Vellecco","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, I-80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarosaria","family":"Bucci","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, I-80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6618-2949","authenticated-orcid":false,"given":"Daniela","family":"Marasco","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, I-80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0274-4671","authenticated-orcid":false,"given":"Elisabetta","family":"Panza","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, I-80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1724-7128","authenticated-orcid":false,"given":"Veronica","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, I-80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8805-6348","authenticated-orcid":false,"given":"Aldo","family":"Galeone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, I-80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"704077","DOI":"10.3389\/fbioe.2021.704077","article-title":"Systematic Evolution of Ligands by Exponential Enrichment Technologies and Aptamer-Based Applications: Recent Progress and Challenges in Precision Medicine of Infectious Diseases","volume":"9","author":"Xu","year":"2021","journal-title":"Front. 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