Recognition of ATT Triplex and DNA:RNA Hybrid Structures by Benzothiazole Ligands
Interactions of an array of nucleic acid structures with a small series of benzothiazole ligands (bis-benzothiazolyl-pyridines—group 1, 2-thienyl/2-benzothienyl-substituted 6-(2-imidazolinyl)benzothiazoles—group 2, and three 2-aryl/heteroaryl-substituted 6-(2-imidazolinyl)benzothiazoles—group 3) wer...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-02-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/12/3/374 |
| _version_ | 1797472705381924864 |
|---|---|
| author | Iva Zonjić Lidija-Marija Tumir Ivo Crnolatac Filip Šupljika Livio Racané Sanja Tomić Marijana Radić Stojković |
| author_facet | Iva Zonjić Lidija-Marija Tumir Ivo Crnolatac Filip Šupljika Livio Racané Sanja Tomić Marijana Radić Stojković |
| author_sort | Iva Zonjić |
| collection | DOAJ |
| description | Interactions of an array of nucleic acid structures with a small series of benzothiazole ligands (bis-benzothiazolyl-pyridines—group 1, 2-thienyl/2-benzothienyl-substituted 6-(2-imidazolinyl)benzothiazoles—group 2, and three 2-aryl/heteroaryl-substituted 6-(2-imidazolinyl)benzothiazoles—group 3) were screened by competition dialysis. Due to the involvement of DNA:RNA hybrids and triplex helices in many essential functions in cells, this study’s main aim is to detect benzothiazole-based moieties with selective binding or spectroscopic response to these nucleic structures compared to regular (non-hybrid) DNA and RNA duplexes and single-stranded forms. Complexes of nucleic acids and benzothiazoles, selected by this method, were characterized by UV/Vis, fluorescence and circular dichroism (CD) spectroscopy, isothermal titration calorimetry, and molecular modeling. Two compounds (<b>1</b> and <b>6</b>) from groups 1 and 2 demonstrated the highest affinities against 13 nucleic acid structures, while another compound (<b>5</b>) from group 2, despite lower affinities, yielded higher selectivity among studied compounds. Compound <b>1</b> significantly inhibited RNase H. Compound <b>6</b> could differentiate between B- (binding of <b>6</b> dimers inside minor groove) and A-type (intercalation) helices by an induced CD signal, while both <b>5</b> and <b>6</b> selectively stabilized ATT triplex in regard to AT duplex. Compound <b>3</b> induced strong condensation-like changes in CD spectra of AT-rich DNA sequences. |
| first_indexed | 2024-03-09T20:05:01Z |
| format | Article |
| id | doaj.art-9f2896c85ab943179f4d8525d92a6ad6 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T20:05:01Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-9f2896c85ab943179f4d8525d92a6ad62023-11-24T00:35:01ZengMDPI AGBiomolecules2218-273X2022-02-0112337410.3390/biom12030374Recognition of ATT Triplex and DNA:RNA Hybrid Structures by Benzothiazole LigandsIva Zonjić0Lidija-Marija Tumir1Ivo Crnolatac2Filip Šupljika3Livio Racané4Sanja Tomić5Marijana Radić Stojković6Laboratory for Biomolecular Interactions and Spectroscopy, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, CroatiaLaboratory for Biomolecular Interactions and Spectroscopy, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, CroatiaLaboratory for Biomolecular Interactions and Spectroscopy, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, CroatiaFaculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, CroatiaDepartment of Applied Chemistry, Faculty of Textile Technology, University of Zagreb, Prilaz Baruna Filipovića 28a, 10000 Zagreb, CroatiaLaboratory for Protein Biochemistry and Molecular Modelling, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, CroatiaLaboratory for Biomolecular Interactions and Spectroscopy, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, CroatiaInteractions of an array of nucleic acid structures with a small series of benzothiazole ligands (bis-benzothiazolyl-pyridines—group 1, 2-thienyl/2-benzothienyl-substituted 6-(2-imidazolinyl)benzothiazoles—group 2, and three 2-aryl/heteroaryl-substituted 6-(2-imidazolinyl)benzothiazoles—group 3) were screened by competition dialysis. Due to the involvement of DNA:RNA hybrids and triplex helices in many essential functions in cells, this study’s main aim is to detect benzothiazole-based moieties with selective binding or spectroscopic response to these nucleic structures compared to regular (non-hybrid) DNA and RNA duplexes and single-stranded forms. Complexes of nucleic acids and benzothiazoles, selected by this method, were characterized by UV/Vis, fluorescence and circular dichroism (CD) spectroscopy, isothermal titration calorimetry, and molecular modeling. Two compounds (<b>1</b> and <b>6</b>) from groups 1 and 2 demonstrated the highest affinities against 13 nucleic acid structures, while another compound (<b>5</b>) from group 2, despite lower affinities, yielded higher selectivity among studied compounds. Compound <b>1</b> significantly inhibited RNase H. Compound <b>6</b> could differentiate between B- (binding of <b>6</b> dimers inside minor groove) and A-type (intercalation) helices by an induced CD signal, while both <b>5</b> and <b>6</b> selectively stabilized ATT triplex in regard to AT duplex. Compound <b>3</b> induced strong condensation-like changes in CD spectra of AT-rich DNA sequences.https://www.mdpi.com/2218-273X/12/3/374benzothiazolescompetition dialysisDNA:RNA hybridsATT triplexcircular dichroism spectroscopyRNase H |
| spellingShingle | Iva Zonjić Lidija-Marija Tumir Ivo Crnolatac Filip Šupljika Livio Racané Sanja Tomić Marijana Radić Stojković Recognition of ATT Triplex and DNA:RNA Hybrid Structures by Benzothiazole Ligands Biomolecules benzothiazoles competition dialysis DNA:RNA hybrids ATT triplex circular dichroism spectroscopy RNase H |
| title | Recognition of ATT Triplex and DNA:RNA Hybrid Structures by Benzothiazole Ligands |
| title_full | Recognition of ATT Triplex and DNA:RNA Hybrid Structures by Benzothiazole Ligands |
| title_fullStr | Recognition of ATT Triplex and DNA:RNA Hybrid Structures by Benzothiazole Ligands |
| title_full_unstemmed | Recognition of ATT Triplex and DNA:RNA Hybrid Structures by Benzothiazole Ligands |
| title_short | Recognition of ATT Triplex and DNA:RNA Hybrid Structures by Benzothiazole Ligands |
| title_sort | recognition of att triplex and dna rna hybrid structures by benzothiazole ligands |
| topic | benzothiazoles competition dialysis DNA:RNA hybrids ATT triplex circular dichroism spectroscopy RNase H |
| url | https://www.mdpi.com/2218-273X/12/3/374 |
| work_keys_str_mv | AT ivazonjic recognitionofatttriplexanddnarnahybridstructuresbybenzothiazoleligands AT lidijamarijatumir recognitionofatttriplexanddnarnahybridstructuresbybenzothiazoleligands AT ivocrnolatac recognitionofatttriplexanddnarnahybridstructuresbybenzothiazoleligands AT filipsupljika recognitionofatttriplexanddnarnahybridstructuresbybenzothiazoleligands AT livioracane recognitionofatttriplexanddnarnahybridstructuresbybenzothiazoleligands AT sanjatomic recognitionofatttriplexanddnarnahybridstructuresbybenzothiazoleligands AT marijanaradicstojkovic recognitionofatttriplexanddnarnahybridstructuresbybenzothiazoleligands |