Synthesis and Telomeric G-Quadruplex-Stabilizing Ability of Macrocyclic Hexaoxazoles Bearing Three Side Chains

G-quadruplexes (G4s), which are structures formed in guanine-rich regions of DNA, are involved in a variety of significant biological functions, and therefore “sequence-dependent” selective G4-stabilizing agents are required as tools to investigate and modulate these functions. Here, we describe the...

Descripción completa

Detalles Bibliográficos
Autores principales: Ma, Yue, Iida, Keisuke, Sasaki, Shogo, Hirokawa, Takatsugu, Heddi, Brahim, Phan, Anh Tuân, Nagasawa, Kazuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358838/
https://www.ncbi.nlm.nih.gov/pubmed/30642002
http://dx.doi.org/10.3390/molecules24020263
_version_ 1783392081076551680
author Ma, Yue
Iida, Keisuke
Sasaki, Shogo
Hirokawa, Takatsugu
Heddi, Brahim
Phan, Anh Tuân
Nagasawa, Kazuo
author_facet Ma, Yue
Iida, Keisuke
Sasaki, Shogo
Hirokawa, Takatsugu
Heddi, Brahim
Phan, Anh Tuân
Nagasawa, Kazuo
author_sort Ma, Yue
collection PubMed
description G-quadruplexes (G4s), which are structures formed in guanine-rich regions of DNA, are involved in a variety of significant biological functions, and therefore “sequence-dependent” selective G4-stabilizing agents are required as tools to investigate and modulate these functions. Here, we describe the synthesis of a new series of macrocyclic hexaoxazole-type G4 ligand (6OTD) bearing three side chains. One of these ligands, 5b, stabilizes telomeric G4 preferentially over the G4-forming DNA sequences of c-kit and K-ras, due to the interaction of its piperazinylalkyl side chain with the groove of telomeric G4.
format Online
Article
Text
id pubmed-6358838
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-63588382019-02-06 Synthesis and Telomeric G-Quadruplex-Stabilizing Ability of Macrocyclic Hexaoxazoles Bearing Three Side Chains Ma, Yue Iida, Keisuke Sasaki, Shogo Hirokawa, Takatsugu Heddi, Brahim Phan, Anh Tuân Nagasawa, Kazuo Molecules Article G-quadruplexes (G4s), which are structures formed in guanine-rich regions of DNA, are involved in a variety of significant biological functions, and therefore “sequence-dependent” selective G4-stabilizing agents are required as tools to investigate and modulate these functions. Here, we describe the synthesis of a new series of macrocyclic hexaoxazole-type G4 ligand (6OTD) bearing three side chains. One of these ligands, 5b, stabilizes telomeric G4 preferentially over the G4-forming DNA sequences of c-kit and K-ras, due to the interaction of its piperazinylalkyl side chain with the groove of telomeric G4. MDPI 2019-01-11 /pmc/articles/PMC6358838/ /pubmed/30642002 http://dx.doi.org/10.3390/molecules24020263 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ma, Yue
Iida, Keisuke
Sasaki, Shogo
Hirokawa, Takatsugu
Heddi, Brahim
Phan, Anh Tuân
Nagasawa, Kazuo
Synthesis and Telomeric G-Quadruplex-Stabilizing Ability of Macrocyclic Hexaoxazoles Bearing Three Side Chains
title Synthesis and Telomeric G-Quadruplex-Stabilizing Ability of Macrocyclic Hexaoxazoles Bearing Three Side Chains
title_full Synthesis and Telomeric G-Quadruplex-Stabilizing Ability of Macrocyclic Hexaoxazoles Bearing Three Side Chains
title_fullStr Synthesis and Telomeric G-Quadruplex-Stabilizing Ability of Macrocyclic Hexaoxazoles Bearing Three Side Chains
title_full_unstemmed Synthesis and Telomeric G-Quadruplex-Stabilizing Ability of Macrocyclic Hexaoxazoles Bearing Three Side Chains
title_short Synthesis and Telomeric G-Quadruplex-Stabilizing Ability of Macrocyclic Hexaoxazoles Bearing Three Side Chains
title_sort synthesis and telomeric g-quadruplex-stabilizing ability of macrocyclic hexaoxazoles bearing three side chains
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358838/
https://www.ncbi.nlm.nih.gov/pubmed/30642002
http://dx.doi.org/10.3390/molecules24020263
work_keys_str_mv AT mayue synthesisandtelomericgquadruplexstabilizingabilityofmacrocyclichexaoxazolesbearingthreesidechains
AT iidakeisuke synthesisandtelomericgquadruplexstabilizingabilityofmacrocyclichexaoxazolesbearingthreesidechains
AT sasakishogo synthesisandtelomericgquadruplexstabilizingabilityofmacrocyclichexaoxazolesbearingthreesidechains
AT hirokawatakatsugu synthesisandtelomericgquadruplexstabilizingabilityofmacrocyclichexaoxazolesbearingthreesidechains
AT heddibrahim synthesisandtelomericgquadruplexstabilizingabilityofmacrocyclichexaoxazolesbearingthreesidechains
AT phananhtuan synthesisandtelomericgquadruplexstabilizingabilityofmacrocyclichexaoxazolesbearingthreesidechains
AT nagasawakazuo synthesisandtelomericgquadruplexstabilizingabilityofmacrocyclichexaoxazolesbearingthreesidechains

Ejemplares similares