Development of fluorescent probes specific for parallel-stranded G-quadruplexes by a library approach

Area of Science:

• Medicinal Chemistry
• Biophysical Chemistry
• Molecular Biology

Background:

• G-quadruplexes are four-stranded DNA structures implicated in various biological processes.
• Identifying specific G-quadruplex topologies is crucial for understanding their function and developing targeted therapeutics.
• Existing methods for G-quadruplex detection often lack the required sensitivity or selectivity for complex structures.

Purpose of the Study:

• To discover and characterize a novel fluorescent probe for identifying a specific subset of parallel G-quadruplexes.
• To develop a tool for sensitive and selective detection of G-quadruplexes with propeller loops across three tetrad layers.

Main Methods:

• Construction of a 241-membered cyanine-based compound library using combinatorial chemistry.
• High-throughput screening of the library to identify fluorescent probes with desired binding properties.
• Characterization of the lead compound (CyC-M716) for its sensitivity and selectivity towards target G-quadruplexes.

Main Results:

• Discovery of a novel cyanine-based fluorescent probe, designated CyC-M716.
• CyC-M716 demonstrates high sensitivity and selectivity in identifying parallel G-quadruplexes.
• The probe effectively detects G-quadruplexes featuring propeller loops extending over three tetrad layers.

Conclusions:

• The novel fluorescent probe CyC-M716 represents a significant advancement in G-quadruplex detection technology.
• This probe offers a powerful tool for studying the biological roles of specific G-quadruplex structures.
• CyC-M716 has potential applications in diagnostics and drug discovery targeting G-quadruplexes.