New Modified Deoxythymine with Dibranched Tetraethylene Glycol Stabilizes G-Quadruplex Structures
Methods for stabilizing G-quadruplex formation is a promising therapeutic approach for cancer treatment and other biomedical applications because stable G-quadruplexes efficiently inhibit biological reactions. Oligo and polyethylene glycols are promising biocompatible compounds, and we have shown th...
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doaj-f0bc9c3d319c4320a9d22e46476ccb042020-11-25T02:20:24ZengMDPI AGMolecules1420-30492020-02-0125370510.3390/molecules25030705molecules25030705New Modified Deoxythymine with Dibranched Tetraethylene Glycol Stabilizes G-Quadruplex StructuresHisae Tateishi-Karimata0Tatsuya Ohyama1Takahiro Muraoka2Shigenori Tanaka3Kazushi Kinbara4Naoki Sugimoto5Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, JapanFrontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, JapanInstitute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, JapanDepartment of Computational Science, Graduate School of System Informatics, Kobe University, 1-1, Rokkodai, Nada-ku, Kobe 657-8501, JapanSchool of Life Science and Technology, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama 226-8501, JapanFrontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, JapanMethods for stabilizing G-quadruplex formation is a promising therapeutic approach for cancer treatment and other biomedical applications because stable G-quadruplexes efficiently inhibit biological reactions. Oligo and polyethylene glycols are promising biocompatible compounds, and we have shown that linear oligoethylene glycols can stabilize G-quadruplexes. Here, we developed a new modified deoxythymine with dibranched or tribranched tetraethylene glycol (TEG) and incorporated these TEG-modified deoxythymines into a loop region that forms an antiparallel G-quadruplex. We analyzed the stability of the modified G-quadruplexes, and the results showed that the tribranched TEG destabilized G-quadruplexes through entropic contributions, likely through steric hindrance. Interestingly, the dibranched TEG modification increased G-quadruplex stability relative to the unmodified DNA structures due to favorable enthalpic contributions. Molecular dynamics calculations suggested that dibranched TEG interacts with the G-quadruplex through hydrogen bonding and CH-π interactions. Moreover, these branched TEG-modified deoxythymine protected the DNA oligonucleotides from degradation by various nucleases in human serum. By taking advantage of the unique interactions between DNA and branched TEG, advanced DNA materials can be developed that affect the regulation of DNA structure.https://www.mdpi.com/1420-3049/25/3/705branched tetraethylene glycolg-quadruplexstabilitymodified nucleic acidch-π interactions |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hisae Tateishi-Karimata Tatsuya Ohyama Takahiro Muraoka Shigenori Tanaka Kazushi Kinbara Naoki Sugimoto |
spellingShingle |
Hisae Tateishi-Karimata Tatsuya Ohyama Takahiro Muraoka Shigenori Tanaka Kazushi Kinbara Naoki Sugimoto New Modified Deoxythymine with Dibranched Tetraethylene Glycol Stabilizes G-Quadruplex Structures Molecules branched tetraethylene glycol g-quadruplex stability modified nucleic acid ch-π interactions |
author_facet |
Hisae Tateishi-Karimata Tatsuya Ohyama Takahiro Muraoka Shigenori Tanaka Kazushi Kinbara Naoki Sugimoto |
author_sort |
Hisae Tateishi-Karimata |
title |
New Modified Deoxythymine with Dibranched Tetraethylene Glycol Stabilizes G-Quadruplex Structures |
title_short |
New Modified Deoxythymine with Dibranched Tetraethylene Glycol Stabilizes G-Quadruplex Structures |
title_full |
New Modified Deoxythymine with Dibranched Tetraethylene Glycol Stabilizes G-Quadruplex Structures |
title_fullStr |
New Modified Deoxythymine with Dibranched Tetraethylene Glycol Stabilizes G-Quadruplex Structures |
title_full_unstemmed |
New Modified Deoxythymine with Dibranched Tetraethylene Glycol Stabilizes G-Quadruplex Structures |
title_sort |
new modified deoxythymine with dibranched tetraethylene glycol stabilizes g-quadruplex structures |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2020-02-01 |
description |
Methods for stabilizing G-quadruplex formation is a promising therapeutic approach for cancer treatment and other biomedical applications because stable G-quadruplexes efficiently inhibit biological reactions. Oligo and polyethylene glycols are promising biocompatible compounds, and we have shown that linear oligoethylene glycols can stabilize G-quadruplexes. Here, we developed a new modified deoxythymine with dibranched or tribranched tetraethylene glycol (TEG) and incorporated these TEG-modified deoxythymines into a loop region that forms an antiparallel G-quadruplex. We analyzed the stability of the modified G-quadruplexes, and the results showed that the tribranched TEG destabilized G-quadruplexes through entropic contributions, likely through steric hindrance. Interestingly, the dibranched TEG modification increased G-quadruplex stability relative to the unmodified DNA structures due to favorable enthalpic contributions. Molecular dynamics calculations suggested that dibranched TEG interacts with the G-quadruplex through hydrogen bonding and CH-π interactions. Moreover, these branched TEG-modified deoxythymine protected the DNA oligonucleotides from degradation by various nucleases in human serum. By taking advantage of the unique interactions between DNA and branched TEG, advanced DNA materials can be developed that affect the regulation of DNA structure. |
topic |
branched tetraethylene glycol g-quadruplex stability modified nucleic acid ch-π interactions |
url |
https://www.mdpi.com/1420-3049/25/3/705 |
work_keys_str_mv |
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