Studies on the Interactions of 3,11-Difluoro-6,8,13-trimethyl-8<i>H</i>-quino[4,3,2-<i>kl</i>]acridinium and Insulin with the Quadruplex-Forming Oligonucleotide Sequence a2 from the Insulin-Linked Polymorphic Region
Recently, several quadruplex-DNA-forming sequences have been identified in the insulin-linked polymorphic region (ILPR), which is a guanine-rich oligonucleotide sequence in the promoter region of insulin. The formation of this non-canonical quadruplex DNA (G4-DNA) has been shown to be involved in th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/21/6595 |
| _version_ | 1797512046594490368 |
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| author | Peter Jonas Wickhorst Heiko Ihmels Thomas Paululat |
| author_facet | Peter Jonas Wickhorst Heiko Ihmels Thomas Paululat |
| author_sort | Peter Jonas Wickhorst |
| collection | DOAJ |
| description | Recently, several quadruplex-DNA-forming sequences have been identified in the insulin-linked polymorphic region (ILPR), which is a guanine-rich oligonucleotide sequence in the promoter region of insulin. The formation of this non-canonical quadruplex DNA (G4-DNA) has been shown to be involved in the biological activity of the ILPR, specifically with regard to its interplay with insulin. In this context, this contribution reports on the investigation of the association of the quadruplex-forming ILPR sequence <b>a2</b> with insulin as well as with the well-known G4-DNA ligand 3,11-difluoro-6,8,13-trimethyl-8<i>H</i>-quino[4,3,2-<i>kl</i>]acridinium (<b>1</b>), also named RHPS4, by optical and NMR spectroscopy. CD- and NMR-spectroscopic measurements confirmed the preferential formation of an antiparallel quadruplex structure of <b>a2</b> with four stacked guanine quartets. Furthermore, ligand <b>1</b> has high affinity toward <b>a2</b> and binds by terminal <i>π</i> stacking to the G1–G11–G15–G25 quartet. In addition, the spectroscopic studies pointed to an association of insulin to the deoxyribose backbone of the loops of <b>a2</b>. |
| first_indexed | 2024-03-10T05:56:21Z |
| format | Article |
| id | doaj.art-f73d9c5a588145f1ae2e619e0e091ca6 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T05:56:21Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f73d9c5a588145f1ae2e619e0e091ca62023-11-22T21:23:39ZengMDPI AGMolecules1420-30492021-10-012621659510.3390/molecules26216595Studies on the Interactions of 3,11-Difluoro-6,8,13-trimethyl-8<i>H</i>-quino[4,3,2-<i>kl</i>]acridinium and Insulin with the Quadruplex-Forming Oligonucleotide Sequence a2 from the Insulin-Linked Polymorphic RegionPeter Jonas Wickhorst0Heiko Ihmels1Thomas Paululat2Department of Chemistry-Biology, Center of Micro- and Nanochemistry and (Bio-)Technology (Cµ), University of Siegen, Adolf-Reichwein-Str. 2, 57068 Siegen, GermanyDepartment of Chemistry-Biology, Center of Micro- and Nanochemistry and (Bio-)Technology (Cµ), University of Siegen, Adolf-Reichwein-Str. 2, 57068 Siegen, GermanyDepartment of Chemistry-Biology, Center of Micro- and Nanochemistry and (Bio-)Technology (Cµ), University of Siegen, Adolf-Reichwein-Str. 2, 57068 Siegen, GermanyRecently, several quadruplex-DNA-forming sequences have been identified in the insulin-linked polymorphic region (ILPR), which is a guanine-rich oligonucleotide sequence in the promoter region of insulin. The formation of this non-canonical quadruplex DNA (G4-DNA) has been shown to be involved in the biological activity of the ILPR, specifically with regard to its interplay with insulin. In this context, this contribution reports on the investigation of the association of the quadruplex-forming ILPR sequence <b>a2</b> with insulin as well as with the well-known G4-DNA ligand 3,11-difluoro-6,8,13-trimethyl-8<i>H</i>-quino[4,3,2-<i>kl</i>]acridinium (<b>1</b>), also named RHPS4, by optical and NMR spectroscopy. CD- and NMR-spectroscopic measurements confirmed the preferential formation of an antiparallel quadruplex structure of <b>a2</b> with four stacked guanine quartets. Furthermore, ligand <b>1</b> has high affinity toward <b>a2</b> and binds by terminal <i>π</i> stacking to the G1–G11–G15–G25 quartet. In addition, the spectroscopic studies pointed to an association of insulin to the deoxyribose backbone of the loops of <b>a2</b>.https://www.mdpi.com/1420-3049/26/21/6595DNA recognitionILPRspectroscopic methods |
| spellingShingle | Peter Jonas Wickhorst Heiko Ihmels Thomas Paululat Studies on the Interactions of 3,11-Difluoro-6,8,13-trimethyl-8<i>H</i>-quino[4,3,2-<i>kl</i>]acridinium and Insulin with the Quadruplex-Forming Oligonucleotide Sequence a2 from the Insulin-Linked Polymorphic Region Molecules DNA recognition ILPR spectroscopic methods |
| title | Studies on the Interactions of 3,11-Difluoro-6,8,13-trimethyl-8<i>H</i>-quino[4,3,2-<i>kl</i>]acridinium and Insulin with the Quadruplex-Forming Oligonucleotide Sequence a2 from the Insulin-Linked Polymorphic Region |
| title_full | Studies on the Interactions of 3,11-Difluoro-6,8,13-trimethyl-8<i>H</i>-quino[4,3,2-<i>kl</i>]acridinium and Insulin with the Quadruplex-Forming Oligonucleotide Sequence a2 from the Insulin-Linked Polymorphic Region |
| title_fullStr | Studies on the Interactions of 3,11-Difluoro-6,8,13-trimethyl-8<i>H</i>-quino[4,3,2-<i>kl</i>]acridinium and Insulin with the Quadruplex-Forming Oligonucleotide Sequence a2 from the Insulin-Linked Polymorphic Region |
| title_full_unstemmed | Studies on the Interactions of 3,11-Difluoro-6,8,13-trimethyl-8<i>H</i>-quino[4,3,2-<i>kl</i>]acridinium and Insulin with the Quadruplex-Forming Oligonucleotide Sequence a2 from the Insulin-Linked Polymorphic Region |
| title_short | Studies on the Interactions of 3,11-Difluoro-6,8,13-trimethyl-8<i>H</i>-quino[4,3,2-<i>kl</i>]acridinium and Insulin with the Quadruplex-Forming Oligonucleotide Sequence a2 from the Insulin-Linked Polymorphic Region |
| title_sort | studies on the interactions of 3 11 difluoro 6 8 13 trimethyl 8 i h i quino 4 3 2 i kl i acridinium and insulin with the quadruplex forming oligonucleotide sequence a2 from the insulin linked polymorphic region |
| topic | DNA recognition ILPR spectroscopic methods |
| url | https://www.mdpi.com/1420-3049/26/21/6595 |
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