Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/139379
Title: Simultaneous binding of hybrid molecules constructed with dual DNA-binding components to a G-quadruplex and its proximal duplex
Authors: Asamitsu, Sefan
Obata, Shunsuke
Phan, Anh Tuân
Hashiya, Kaori
Bando, Toshikazu
Sugiyama, Hiroshi
Keywords: Science::Biological sciences
Issue Date: 2018
Source: 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
Journal: Chemistry - A European Journal
Abstract: 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.
URI: https://hdl.handle.net/10356/139379
ISSN: 0947-6539
DOI: 10.1002/chem.201705945
Rights: 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].
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SPMS Journal Articles

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