G-Quadruplexes as An Alternative Recognition Element in Disease-Related Target Sensing

Abstract

G-quadruplexes are made up of guanine-rich RNA and DNA sequences capable of forming noncanonical nucleic acid secondary structures. The base-specific sterical configuration of G-quadruplexes allows the stacked G-tetrads to bind certain planar molecules like hemin (iron (III)-protoporphyrin IX) to regulate enzymatic-like functions such as peroxidase-mimicking activity, hence the use of the term DNAzyme/RNAzyme. This ability has been widely touted as a suitable substitute to conventional enzymatic reporter systems in diagnostics. This review will provide a brief overview of the G-quadruplex architecture as well as the many forms of reporter systems ranging from absorbance to luminescence readouts in various platforms. Furthermore, some challenges and improvements that have been introduced to improve the application of G-quadruplex in diagnostics will be highlighted. As the field of diagnostics has evolved to apply different detection systems, the need for alternative reporter systems such as G-quadruplexes is also paramount.

The Red Color of Life Transformed – Synthetic Advances and Emerging Applications of Protoporphyrin IX in Chemical Biology

“…Guanine‐rich nucleic acid‐segments form particular secondary structures in vivo which function as regulators of genome and telomere stability as well as gene activity. [18a], In such sequences the formation of guanine‐quartets (G‐quartets) via Hoogsteen base pairing can lead to the arrangement of the respective DNA or RNA sequences in four‐stranded helices, the so‐called G‐quadruplexes (Figure ) . Together with other molecules, these motifs have drawn attention as biochemical tools for in vitro applications such as DNAzymes to catalyze redox reactions in a peroxidase‐like fashion, as well as for the detection of enzymatic activity, nucleic acids, proteins, small molecules and metal ions ,…”

“…In contrast, Na + ‐stabilized G‐quadruplexes preferentially adopt a parallel conformation of the strands (Figure ). [83a], Moreover, the G‐quartet constitutes a plane of aromatic moieties that can interact with aromatic molecules via π‐π‐interactions. Such interactions can be used to detect G‐quadruplex formation or to form functional entities such as DNAzymes.…”

“…Among the compounds with G‐quadruplex binding abilities are tetrapyrroles such as phthalocyanines and porphyrins. [18a], Notably, hemin binding for generation of DNAzymes with peroxidase‐like activity and for the development of molecular sensing devices has found widespread attention and has been discussed in several reviews , ,. [86a], Herein, we will focus on the use of PPIX and its Zn(II) complex in conjunction with G‐quadruplex structures as biosensors.…”

“…The inherent property of G‐quadruplexes to take on different conformations of different stabilities upon binding to various metal ions has been used for fluorescent detection of metals with PPIX as a signal reporter. [83a], [85b], , , [94c], For example, Li et al analyzed the ability of PPIX to bind to the G‐quadruplex‐forming DNA sequence PS2.M and showed that PPIX preferentially binds parallel G‐quadruplex structures with an about 100‐fold selectivity over duplexes and antiparallel G‐quadruplexes. DNA binding resulted in a 10‐fold increase in the porphyrin fluorescence.…”

Structural Features of Nucleoprotein CST/Shelterin Complex Involved in the Telomere Maintenance and Its Association with Disease Mutations

“…To come up with novel possible ways to target these complexes, some hypothetical approaches are outlined in Figure 6. Telomerase/telomere or inhibitors of telomere maintaining proteins might not only directly limit the growth of the cancerous cells, but could become more effective using in a synergistic fashion with existing therapeutic modalities such as with chemotherapeutic agents and anti-angiogenic agents [213,255,256]. Figure 6.…”