Illuminating the G-Quadruplex: A Review on Fluorescent Probes for Detecting Polymorphic G-Quartet DNA Structures

Abstract: Modulating crucial biological processes such as gene regulation, aging, and relationship to globally important human health issues such as cancer has significantly brought considerable attention to G-quadruplex over the past few decades. As the impact of Gquadruplex emerges on so many biological roles, cancer prognosis and pathogenesis have not been fully understood, and selective small molecular binders with suitable chemical, photophysical and biological properties are potentially applicable biophysical tools for tracking Gquadruplex functions. The chemical properties include suitable water solubility, liphophilicity, etc., and the photophysical properties include excitation, emission, stoke-shift, lifetime, quantum yield, and measurable, selective changes of former photophysical parameters within the ideal spectral window upon interaction with the target. The biological properties include; toxicity, cellular infiltration, and selective binding with G-quadruplex over non-specific targets (e.g., duplex DNA, RNA, non-specific biomolecules etc.) in the complex cellular matrix. The development of G-quadruplex-selective probes, therefore, continues to be an important but challenging task for molecular therapeutic, diagnostic, imaging, and sensing applications. In this review, we have classified and summarized several classes of probes; carbocyanine, porphyrins, ethidium, carbazoles, acridines, tripodal or tetrapodal probes, pyrimidine carboxamides, tianguleniums, anthraquinones, polyaromatic hydrocarbons, BODIPY dyes, berberines, acetones and their derivatives for the variation of selectivity, photophysical, and biological properties with respect to the structural modifications, which ultimately provide helpful guidance for designing novel probes with optimal characteristics.