Synthesis and telomeric G-quadruplex-stabilizing ability of macrocyclic hexaoxazoles bearing three side chains

• Main Authors: Ma, Yue, Iida, Keisuke, Sasaki, Shogo, Hirokawa, Takatsugu, Heddi, Brahim, Nagasawa, Kazuo, Phan, Anh Tuân
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2019
• Subjects: DRNTU::Science::Physics; G-Quadruplex; Macrocyclic Oxazole
• Online Access: https://hdl.handle.net/10356/105834; http://hdl.handle.net/10220/48766
• Institution: Nanyang Technological University

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.