Simultaneous binding of hybrid molecules constructed with dual DNA-binding components to a G-quadruplex and its proximal duplex
A G-quadruplex (quadruplex) is a nucleic acid secondary structure adopted by guanine-rich sequences and is considered to be relevant to various pharmacological and biological contexts. Although a number of researchers have endeavored to discover and develop quadruplex-interactive molecules, poor lig...
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sg-ntu-dr.10356-1393792020-05-19T05:53:08Z Simultaneous binding of hybrid molecules constructed with dual DNA-binding components to a G-quadruplex and its proximal duplex Asamitsu, Sefan Obata, Shunsuke Phan, Anh Tuân Hashiya, Kaori Bando, Toshikazu Sugiyama, Hiroshi School of Physical and Mathematical Sciences Science::Biological sciences Dual DNA-binding Components G-quadruplexes A G-quadruplex (quadruplex) is a nucleic acid secondary structure adopted by guanine-rich sequences and is considered to be relevant to various pharmacological and biological contexts. Although a number of researchers have endeavored to discover and develop quadruplex-interactive molecules, poor ligand designability originating from topological similarity of the skeleton of diverse quadruplexes has remained a bottleneck for gaining specificity for individual quadruplexes. This work reports on hybrid molecules that were constructed with dual DNA-binding components, a cyclic imidazole/lysine polyamide (cIKP), and a hairpin pyrrole/imidazole polyamide (hPIP), with the aim toward specific quadruplex targeting by reading out the local duplex DNA sequence adjacent to designated quadruplexes in the genome. By means of circular dichroism (CD), fluorescence resonance energy transfer (FRET), surface plasmon resonance (SPR), and NMR techniques, we showed the dual and simultaneous recognition of the respective segment via hybrid molecules, and the synergistic and mutual effect of each binding component that was appropriately linked on higher binding affinity and modest sequence specificity. Monitoring quadruplex and duplex imino protons of the quadruplex/duplex motif titrated with hybrid molecules clearly revealed distinct features of the binding of hybrid molecules to the respective segments upon their simultaneous recognition. A series of the systematic and detailed binding assays described here showed that the concept of simultaneous recognition of quadruplex and its proximal duplex by hybrid molecules constructed with the dual DNA-binding components may provide a new strategy for ligand design, enabling targeting of a large variety of designated quadruplexes at specific genome locations. MOE (Min. of Education, S’pore) 2020-05-19T05:53:08Z 2020-05-19T05:53:08Z 2018 Journal Article Asamitsu, S., Obata, S., Phan, A. T., Hashiya, K., Bando, T., & Sugiyama, H. (2018). Simultaneous binding of hybrid molecules constructed with dual DNA-binding components to a G-quadruplex and its proximal duplex. Chemistry - A European Journal, 24(17), 4428-4435. doi:10.1002/chem.201705945 0947-6539 https://hdl.handle.net/10356/139379 10.1002/chem.201705945 29380465 2-s2.0-85042399427 17 24 4428 4435 en Chemistry - A European Journal This is the accepted version of the following article: Asamitsu, S., Obata, S., Phan, A. T., Hashiya, K., Bando, T., & Sugiyama, H. (2018). Simultaneous binding of hybrid molecules constructed with dual DNA-binding components to a G-quadruplex and its proximal duplex. Chemistry - A European Journal, 24(17), 4428-4435, which has been published in final form at dx.doi.org/10.1002/chem.201705945. This article may be used for non-commercial purposes in accordance with the Wiley Self-Archiving Policy [https://authorservices.wiley.com/authorresources/Journal-Authors/licensing/self-archiving.html]. |
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Science::Biological sciences Dual DNA-binding Components G-quadruplexes Asamitsu, Sefan Obata, Shunsuke Phan, Anh Tuân Hashiya, Kaori Bando, Toshikazu Sugiyama, Hiroshi Simultaneous binding of hybrid molecules constructed with dual DNA-binding components to a G-quadruplex and its proximal duplex |
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A G-quadruplex (quadruplex) is a nucleic acid secondary structure adopted by guanine-rich sequences and is considered to be relevant to various pharmacological and biological contexts. Although a number of researchers have endeavored to discover and develop quadruplex-interactive molecules, poor ligand designability originating from topological similarity of the skeleton of diverse quadruplexes has remained a bottleneck for gaining specificity for individual quadruplexes. This work reports on hybrid molecules that were constructed with dual DNA-binding components, a cyclic imidazole/lysine polyamide (cIKP), and a hairpin pyrrole/imidazole polyamide (hPIP), with the aim toward specific quadruplex targeting by reading out the local duplex DNA sequence adjacent to designated quadruplexes in the genome. By means of circular dichroism (CD), fluorescence resonance energy transfer (FRET), surface plasmon resonance (SPR), and NMR techniques, we showed the dual and simultaneous recognition of the respective segment via hybrid molecules, and the synergistic and mutual effect of each binding component that was appropriately linked on higher binding affinity and modest sequence specificity. Monitoring quadruplex and duplex imino protons of the quadruplex/duplex motif titrated with hybrid molecules clearly revealed distinct features of the binding of hybrid molecules to the respective segments upon their simultaneous recognition. A series of the systematic and detailed binding assays described here showed that the concept of simultaneous recognition of quadruplex and its proximal duplex by hybrid molecules constructed with the dual DNA-binding components may provide a new strategy for ligand design, enabling targeting of a large variety of designated quadruplexes at specific genome locations. |
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School of Physical and Mathematical Sciences |
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School of Physical and Mathematical Sciences Asamitsu, Sefan Obata, Shunsuke Phan, Anh Tuân Hashiya, Kaori Bando, Toshikazu Sugiyama, Hiroshi |
format |
Article |
author |
Asamitsu, Sefan Obata, Shunsuke Phan, Anh Tuân Hashiya, Kaori Bando, Toshikazu Sugiyama, Hiroshi |
author_sort |
Asamitsu, Sefan |
title |
Simultaneous binding of hybrid molecules constructed with dual DNA-binding components to a G-quadruplex and its proximal duplex |
title_short |
Simultaneous binding of hybrid molecules constructed with dual DNA-binding components to a G-quadruplex and its proximal duplex |
title_full |
Simultaneous binding of hybrid molecules constructed with dual DNA-binding components to a G-quadruplex and its proximal duplex |
title_fullStr |
Simultaneous binding of hybrid molecules constructed with dual DNA-binding components to a G-quadruplex and its proximal duplex |
title_full_unstemmed |
Simultaneous binding of hybrid molecules constructed with dual DNA-binding components to a G-quadruplex and its proximal duplex |
title_sort |
simultaneous binding of hybrid molecules constructed with dual dna-binding components to a g-quadruplex and its proximal duplex |
publishDate |
2020 |
url |
https://hdl.handle.net/10356/139379 |
_version_ |
1681059448818237440 |