Small-molecule selectively recognizes human telomeric G-quadruplex DNA and regulates its conformational switch

Area of Science:

• Biochemistry
• Molecular Biology
• Medicinal Chemistry

Background:

• Human telomeric sequences possess complex structures, posing challenges for pharmaceutical ligand development.
• Inducing or altering G-quadruplex conformations is a key strategy for achieving desired biological effects.

Purpose of the Study:

• To demonstrate a G-quadruplex ligand that selectively binds and regulates conformational switching of human telomeric G-quadruplex structures.
• To investigate the mechanism by which the ligand controls structural transitions.

Main Methods:

• Utilized oxazine750 as a small molecule ligand.
• Studied the induction of parallel G-quadruplex formation from random coil telomeric oligonucleotides.
• Analyzed conformational changes in the presence of Na(+) or K(+) ions.

Main Results:

• Oxazine750 selectively induces parallel G-quadruplex formation even without added cations.
• The ligand effectively overcomes energy barriers to switch G-quadruplex conformations in Na(+) or K(+) solutions.
• The ligand- G-quadruplex size and shape interplay is proposed as the driving force for structural regulation.

Conclusions:

• Oxazine750 demonstrates selective binding and conformational control of human telomeric G-quadruplexes.
• This ligand's properties can stimulate the design of novel G-quadruplex binders for therapeutic and material science applications.