Interaction of isoquinoline alkaloids with pyrimidine motif triplex DNA by mass spectrometry and spectroscopies reveals diverse mechanisms
Isoquinoline alkaloids represent an important class of molecules due to their broad range of pharmacology and clinical utility. Prospective development and use of these alkaloids as effective anticancer agents have elicited great interest. In this study, in order to reveal structure-activity relatio...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023021618 |
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| author | Zhaoyang Xie Sunuo Zhang Yi Wu Jinling Liang Wenbin Yao Ruoning Qu Xiaole Tong Guang Zhang Hongmei Yang |
| author_facet | Zhaoyang Xie Sunuo Zhang Yi Wu Jinling Liang Wenbin Yao Ruoning Qu Xiaole Tong Guang Zhang Hongmei Yang |
| author_sort | Zhaoyang Xie |
| collection | DOAJ |
| description | Isoquinoline alkaloids represent an important class of molecules due to their broad range of pharmacology and clinical utility. Prospective development and use of these alkaloids as effective anticancer agents have elicited great interest. In this study, in order to reveal structure-activity relationship, we present the characterization of bioactive isoquinoline alkaloid-DNA triplex interactions, with particular emphasis on the sequence selectivity and preference of binding to the two types of DNA triplexes, by electrospray ionization mass spectrometry (ESI-MS) and various spectroscopic techniques. The six alkaloids, including coptisine, columbamine, epiberberine, berberrubine, jateorhizine, and fangchinoline, were selected to explore their interactions with the TC and TTT triplex DNA structures. Berberrubine, fangchinoline, coptisine, columbamine, and epiberberine have preference for TC rich DNA sequences compared to TTT rich DNA triplex based on affinity values in MS. The experimental results from different fragmentation modes in tandem MS, subtractive and hyperchromic effects in UV absorption spectra, fluorescence quenching and enhancement in fluorescence spectra, and strong conformational changes in circular dichroism (CD) hinted that the interaction between isoquinoline alkaloid-TC/TTT DNA had diverse mechanisms including at least two different binding modes: the electrostatic binding and the intercalation binding. Interestingly, columbamine, berberrubine, and fangchinoline can stabilize TTT triplex as inferred from optical thermal melting profiles, while it was not the case in TC triplex. These results provide new insights into binding of isoquinoline alkaloids to pyrimidine motif triplex DNA. |
| first_indexed | 2024-04-09T15:18:19Z |
| format | Article |
| id | doaj.art-76914911a3424a21965875c14d3ccb45 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-09T15:18:19Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-76914911a3424a21965875c14d3ccb452023-04-29T14:52:09ZengElsevierHeliyon2405-84402023-04-0194e14954Interaction of isoquinoline alkaloids with pyrimidine motif triplex DNA by mass spectrometry and spectroscopies reveals diverse mechanismsZhaoyang Xie0Sunuo Zhang1Yi Wu2Jinling Liang3Wenbin Yao4Ruoning Qu5Xiaole Tong6Guang Zhang7Hongmei Yang8Northeast Asia Institute of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130021, ChinaSchool of Materials Science and Engineering, Nankai University, Tianjin, 300350, ChinaNortheast Asia Institute of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130021, ChinaCollege of Pharmacy, Changchun University of Chinese Medicine, Changchun, 130117, ChinaCollege of Pharmacy, Changchun University of Chinese Medicine, Changchun, 130117, ChinaChina-Japan Union Hospital of Jilin University, Changchun, 130033, ChinaJilin Jian Yisheng Pharmaceutical Co., Ltd., Jian, 134200, ChinaChina-Japan Union Hospital of Jilin University, Changchun, 130033, China; Corresponding author.Northeast Asia Institute of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130021, China; Corresponding author.Isoquinoline alkaloids represent an important class of molecules due to their broad range of pharmacology and clinical utility. Prospective development and use of these alkaloids as effective anticancer agents have elicited great interest. In this study, in order to reveal structure-activity relationship, we present the characterization of bioactive isoquinoline alkaloid-DNA triplex interactions, with particular emphasis on the sequence selectivity and preference of binding to the two types of DNA triplexes, by electrospray ionization mass spectrometry (ESI-MS) and various spectroscopic techniques. The six alkaloids, including coptisine, columbamine, epiberberine, berberrubine, jateorhizine, and fangchinoline, were selected to explore their interactions with the TC and TTT triplex DNA structures. Berberrubine, fangchinoline, coptisine, columbamine, and epiberberine have preference for TC rich DNA sequences compared to TTT rich DNA triplex based on affinity values in MS. The experimental results from different fragmentation modes in tandem MS, subtractive and hyperchromic effects in UV absorption spectra, fluorescence quenching and enhancement in fluorescence spectra, and strong conformational changes in circular dichroism (CD) hinted that the interaction between isoquinoline alkaloid-TC/TTT DNA had diverse mechanisms including at least two different binding modes: the electrostatic binding and the intercalation binding. Interestingly, columbamine, berberrubine, and fangchinoline can stabilize TTT triplex as inferred from optical thermal melting profiles, while it was not the case in TC triplex. These results provide new insights into binding of isoquinoline alkaloids to pyrimidine motif triplex DNA.http://www.sciencedirect.com/science/article/pii/S2405844023021618Triplex DNAIsoquinoline alkaloidsInteractionMass spectrometrySpectroscopy |
| spellingShingle | Zhaoyang Xie Sunuo Zhang Yi Wu Jinling Liang Wenbin Yao Ruoning Qu Xiaole Tong Guang Zhang Hongmei Yang Interaction of isoquinoline alkaloids with pyrimidine motif triplex DNA by mass spectrometry and spectroscopies reveals diverse mechanisms Heliyon Triplex DNA Isoquinoline alkaloids Interaction Mass spectrometry Spectroscopy |
| title | Interaction of isoquinoline alkaloids with pyrimidine motif triplex DNA by mass spectrometry and spectroscopies reveals diverse mechanisms |
| title_full | Interaction of isoquinoline alkaloids with pyrimidine motif triplex DNA by mass spectrometry and spectroscopies reveals diverse mechanisms |
| title_fullStr | Interaction of isoquinoline alkaloids with pyrimidine motif triplex DNA by mass spectrometry and spectroscopies reveals diverse mechanisms |
| title_full_unstemmed | Interaction of isoquinoline alkaloids with pyrimidine motif triplex DNA by mass spectrometry and spectroscopies reveals diverse mechanisms |
| title_short | Interaction of isoquinoline alkaloids with pyrimidine motif triplex DNA by mass spectrometry and spectroscopies reveals diverse mechanisms |
| title_sort | interaction of isoquinoline alkaloids with pyrimidine motif triplex dna by mass spectrometry and spectroscopies reveals diverse mechanisms |
| topic | Triplex DNA Isoquinoline alkaloids Interaction Mass spectrometry Spectroscopy |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023021618 |
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