{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T19:16:11Z","timestamp":1782587771308,"version":"3.54.5"},"reference-count":102,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T00:00:00Z","timestamp":1590710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>NU172\u2014a 26-mer oligonucleotide able to bind exosite I of human thrombin and inhibit its activity\u2014was the first aptamer to reach Phase II clinical studies as an anticoagulant in heart disease treatments. With the aim of favoring its functional duplex-quadruplex conformation and thus improving its enzymatic stability, as well as its thrombin inhibitory activity, herein a focused set of cyclic NU172 analogues\u2014obtained by connecting its 5\u2032- and 3\u2032-extremities with flexible linkers\u2014was synthesized. Two different chemical approaches were exploited in the cyclization procedure, one based on the oxime ligation method and the other on Cu(I)-assisted azide-alkyne cycloaddition (CuAAC), affording NU172 analogues including circularizing linkers with different length and chemical nature. The resulting cyclic NU172 derivatives were characterized using several biophysical techniques (ultraviolet (UV) and circular dichroism (CD) spectroscopies, gel electrophoresis) and then investigated for their serum resistance and anticoagulant activity in vitro. All the cyclic NU172 analogues showed higher thermal stability and nuclease resistance compared to unmodified NU172. These favorable properties were, however, associated with reduced\u2014even though still significant\u2014anticoagulant activity, suggesting that the conformational constraints introduced upon cyclization were somehow detrimental for protein recognition. These results provide useful information for the design of improved analogues of NU172 and related duplex-quadruplex structures.<\/jats:p>","DOI":"10.3390\/ijms21113860","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T04:09:03Z","timestamp":1591070943000},"page":"3860","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Design, Synthesis and Characterization of Cyclic NU172 Analogues: A Biophysical and Biological Insight"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7182-0757","authenticated-orcid":false,"given":"Claudia","family":"Riccardi","sequence":"first","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, I-80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Meyer","sequence":"additional","affiliation":[{"name":"Institut des Biomole\u0301cules Max Mousseron, Univ. Montpellier, CNRS, ENSCM, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Jacques","family":"Vasseur","sequence":"additional","affiliation":[{"name":"Institut des Biomole\u0301cules Max Mousseron, Univ. Montpellier, CNRS, ENSCM, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Cavasso","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, I-80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8124-6034","authenticated-orcid":false,"given":"Irene","family":"Russo Krauss","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, I-80126 Naples, Italy"},{"name":"CSGI\u2014Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande Interfase, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1105-4237","authenticated-orcid":false,"given":"Luigi","family":"Paduano","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, I-80126 Naples, Italy"},{"name":"CSGI\u2014Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande Interfase, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5077-0028","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Morvan","sequence":"additional","affiliation":[{"name":"Institut des Biomole\u0301cules Max Mousseron, Univ. Montpellier, CNRS, ENSCM, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6295-6911","authenticated-orcid":false,"given":"Daniela","family":"Montesarchio","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, I-80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1111\/j.1538-7836.2005.01363.x","article-title":"Molecular recognition mechanisms of thrombin","volume":"3","author":"Huntington","year":"2005","journal-title":"J. Thromb. 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