Synthesis and Characterization of Bis-Triazolyl-Pyridine Derivatives as Noncanonical DNA-Interacting Compounds
Besides the well-known double-helical conformation, DNA is capable of folding into various noncanonical arrangements, such as G-quadruplexes (G4s) and i-motifs (iMs), whose occurrence in gene promoters, replication origins, and telomeres highlights the breadth of biological processes that they might...
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2021
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oai:doaj.org-article:43b712317829433d906c54d21dabe9e52021-11-11T17:22:42ZSynthesis and Characterization of Bis-Triazolyl-Pyridine Derivatives as Noncanonical DNA-Interacting Compounds10.3390/ijms2221119591422-00671661-6596https://doaj.org/article/43b712317829433d906c54d21dabe9e52021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11959https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Besides the well-known double-helical conformation, DNA is capable of folding into various noncanonical arrangements, such as G-quadruplexes (G4s) and i-motifs (iMs), whose occurrence in gene promoters, replication origins, and telomeres highlights the breadth of biological processes that they might regulate. Particularly, previous studies have reported that G4 and iM structures may play different roles in controlling gene transcription. Anyway, molecular tools able to simultaneously stabilize/destabilize those structures are still needed to shed light on what happens at the biological level. Herein, a multicomponent reaction and a click chemistry functionalization were combined to generate a set of 31 bis-triazolyl-pyridine derivatives which were initially screened by circular dichroism for their ability to interact with different G4 and/or iM DNAs and to affect the thermal stability of these structures. All the compounds were then clustered through multivariate data analysis, based on such capability. The most promising compounds were subjected to a further biophysical and biological characterization, leading to the identification of two molecules simultaneously able to stabilize G4s and destabilize iMs, both in vitro and in living cells.Anna Di PorzioUbaldina GalliJussara AmatoPasquale ZizzaSara IachettiniNunzia IaccarinoSimona MarzanoFederica SantoroDiego BrancaccioAlfonso CarotenutoStefano De TitoAnnamaria BiroccioBruno PaganoGian Cesare TronAntonio RandazzoMDPI AGarticleG-quadruplexi-motifbis-triazolyl-pyridine derivativesclick chemistrybiophysical studyimmunofluorescence microscopyBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11959, p 11959 (2021) |
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| topic |
G-quadruplex i-motif bis-triazolyl-pyridine derivatives click chemistry biophysical study immunofluorescence microscopy Biology (General) QH301-705.5 Chemistry QD1-999 |
| spellingShingle |
G-quadruplex i-motif bis-triazolyl-pyridine derivatives click chemistry biophysical study immunofluorescence microscopy Biology (General) QH301-705.5 Chemistry QD1-999 Anna Di Porzio Ubaldina Galli Jussara Amato Pasquale Zizza Sara Iachettini Nunzia Iaccarino Simona Marzano Federica Santoro Diego Brancaccio Alfonso Carotenuto Stefano De Tito Annamaria Biroccio Bruno Pagano Gian Cesare Tron Antonio Randazzo Synthesis and Characterization of Bis-Triazolyl-Pyridine Derivatives as Noncanonical DNA-Interacting Compounds |
| description |
Besides the well-known double-helical conformation, DNA is capable of folding into various noncanonical arrangements, such as G-quadruplexes (G4s) and i-motifs (iMs), whose occurrence in gene promoters, replication origins, and telomeres highlights the breadth of biological processes that they might regulate. Particularly, previous studies have reported that G4 and iM structures may play different roles in controlling gene transcription. Anyway, molecular tools able to simultaneously stabilize/destabilize those structures are still needed to shed light on what happens at the biological level. Herein, a multicomponent reaction and a click chemistry functionalization were combined to generate a set of 31 bis-triazolyl-pyridine derivatives which were initially screened by circular dichroism for their ability to interact with different G4 and/or iM DNAs and to affect the thermal stability of these structures. All the compounds were then clustered through multivariate data analysis, based on such capability. The most promising compounds were subjected to a further biophysical and biological characterization, leading to the identification of two molecules simultaneously able to stabilize G4s and destabilize iMs, both in vitro and in living cells. |
| format |
article |
| author |
Anna Di Porzio Ubaldina Galli Jussara Amato Pasquale Zizza Sara Iachettini Nunzia Iaccarino Simona Marzano Federica Santoro Diego Brancaccio Alfonso Carotenuto Stefano De Tito Annamaria Biroccio Bruno Pagano Gian Cesare Tron Antonio Randazzo |
| author_facet |
Anna Di Porzio Ubaldina Galli Jussara Amato Pasquale Zizza Sara Iachettini Nunzia Iaccarino Simona Marzano Federica Santoro Diego Brancaccio Alfonso Carotenuto Stefano De Tito Annamaria Biroccio Bruno Pagano Gian Cesare Tron Antonio Randazzo |
| author_sort |
Anna Di Porzio |
| title |
Synthesis and Characterization of Bis-Triazolyl-Pyridine Derivatives as Noncanonical DNA-Interacting Compounds |
| title_short |
Synthesis and Characterization of Bis-Triazolyl-Pyridine Derivatives as Noncanonical DNA-Interacting Compounds |
| title_full |
Synthesis and Characterization of Bis-Triazolyl-Pyridine Derivatives as Noncanonical DNA-Interacting Compounds |
| title_fullStr |
Synthesis and Characterization of Bis-Triazolyl-Pyridine Derivatives as Noncanonical DNA-Interacting Compounds |
| title_full_unstemmed |
Synthesis and Characterization of Bis-Triazolyl-Pyridine Derivatives as Noncanonical DNA-Interacting Compounds |
| title_sort |
synthesis and characterization of bis-triazolyl-pyridine derivatives as noncanonical dna-interacting compounds |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/43b712317829433d906c54d21dabe9e5 |
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