Development of squaraine based G-quadruplex ligands using click chemistry

Abstract The G-quadruplex (G4) structures of nucleic acids are considered to play an intrinsic role in gene expression. To this end, the development of new G4 ligands has attracted extensive research interests towards potential applications as G4-targeted drugs and molecular probes. To date, the maj...

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Autores principales:	Xin Zhang, Yongbiao Wei, Tao Bing, Xiangjun Liu, Nan Zhang, Junyan Wang, Junqing He, Bing Jin, Dihua Shangguan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7e85dac7107b4a2da4b7cc78844c3336
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spelling	oai:doaj.org-article:7e85dac7107b4a2da4b7cc78844c33362021-12-02T16:06:15ZDevelopment of squaraine based G-quadruplex ligands using click chemistry10.1038/s41598-017-04344-x2045-2322https://doaj.org/article/7e85dac7107b4a2da4b7cc78844c33362017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04344-xhttps://doaj.org/toc/2045-2322Abstract The G-quadruplex (G4) structures of nucleic acids are considered to play an intrinsic role in gene expression. To this end, the development of new G4 ligands has attracted extensive research interests towards potential applications as G4-targeted drugs and molecular probes. To date, the majority of G4 ligands have been composed of an extended planar aromatic scaffold that interacts with the terminal G-tetrad plane via π-π interactions, and various side chains that interact with the sugar-phosphate backbone, loops or grooves of the G4 structures. The side chains act to modulate the affinity and selectivity of the G4 ligands, alongside influencing their biodistribution. Here, we present a click chemistry methodology to generate a series of squaraine-based G4 ligand derivatives based on our previously reported G4 probe (named CSTS) but with varing side chains. We find that importantly these new G4 ligand derivatives retain the G4 selectivity, optical properties and low cytotoxicity of CSTS, but exhibit different binding behaviors to G4 structures, and distinct cellular uptake efficiencies. Indeed, of these new complexes, several exhibit much higher affinity and cellular uptake than CSTS. Overall, this novel, facile and highly effective strategy has significant future potential for the high-throughput screening of G4 ligands or probes targeted towards in vivo applications.Xin ZhangYongbiao WeiTao BingXiangjun LiuNan ZhangJunyan WangJunqing HeBing JinDihua ShangguanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xin Zhang Yongbiao Wei Tao Bing Xiangjun Liu Nan Zhang Junyan Wang Junqing He Bing Jin Dihua Shangguan Development of squaraine based G-quadruplex ligands using click chemistry
description	Abstract The G-quadruplex (G4) structures of nucleic acids are considered to play an intrinsic role in gene expression. To this end, the development of new G4 ligands has attracted extensive research interests towards potential applications as G4-targeted drugs and molecular probes. To date, the majority of G4 ligands have been composed of an extended planar aromatic scaffold that interacts with the terminal G-tetrad plane via π-π interactions, and various side chains that interact with the sugar-phosphate backbone, loops or grooves of the G4 structures. The side chains act to modulate the affinity and selectivity of the G4 ligands, alongside influencing their biodistribution. Here, we present a click chemistry methodology to generate a series of squaraine-based G4 ligand derivatives based on our previously reported G4 probe (named CSTS) but with varing side chains. We find that importantly these new G4 ligand derivatives retain the G4 selectivity, optical properties and low cytotoxicity of CSTS, but exhibit different binding behaviors to G4 structures, and distinct cellular uptake efficiencies. Indeed, of these new complexes, several exhibit much higher affinity and cellular uptake than CSTS. Overall, this novel, facile and highly effective strategy has significant future potential for the high-throughput screening of G4 ligands or probes targeted towards in vivo applications.
format	article
author	Xin Zhang Yongbiao Wei Tao Bing Xiangjun Liu Nan Zhang Junyan Wang Junqing He Bing Jin Dihua Shangguan
author_facet	Xin Zhang Yongbiao Wei Tao Bing Xiangjun Liu Nan Zhang Junyan Wang Junqing He Bing Jin Dihua Shangguan
author_sort	Xin Zhang
title	Development of squaraine based G-quadruplex ligands using click chemistry
title_short	Development of squaraine based G-quadruplex ligands using click chemistry
title_full	Development of squaraine based G-quadruplex ligands using click chemistry
title_fullStr	Development of squaraine based G-quadruplex ligands using click chemistry
title_full_unstemmed	Development of squaraine based G-quadruplex ligands using click chemistry
title_sort	development of squaraine based g-quadruplex ligands using click chemistry
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7e85dac7107b4a2da4b7cc78844c3336
work_keys_str_mv	AT xinzhang developmentofsquarainebasedgquadruplexligandsusingclickchemistry AT yongbiaowei developmentofsquarainebasedgquadruplexligandsusingclickchemistry AT taobing developmentofsquarainebasedgquadruplexligandsusingclickchemistry AT xiangjunliu developmentofsquarainebasedgquadruplexligandsusingclickchemistry AT nanzhang developmentofsquarainebasedgquadruplexligandsusingclickchemistry AT junyanwang developmentofsquarainebasedgquadruplexligandsusingclickchemistry AT junqinghe developmentofsquarainebasedgquadruplexligandsusingclickchemistry AT bingjin developmentofsquarainebasedgquadruplexligandsusingclickchemistry AT dihuashangguan developmentofsquarainebasedgquadruplexligandsusingclickchemistry
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Development of squaraine based G-quadruplex ligands using click chemistry

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