Nanoporous Gold Disks Functionalized with Stabilized G-Quadruplex Moieties for Sensing Small Molecules

Guanine-rich nucleic acid sequences can adopt G-quadruplex structures stabilized by layers of four Hoogsteen-paired guanine residues. Quadruplex-prone sequences are found in many regions of human genome and in the telomeres of all eukaryotic organisms. Since small molecules that target G-quadruplexes have been found to be effective telomerase inhibitors, the identification of new specific ligands for G-quadruplexes is emerging as a promising approach to develop new anticancer drugs. Distamycin A is known to bind to AT-rich sequences of duplex DNA, but it has recently been shown to interact also with G-quadruplexes. Here, isothermal titration calorimetry (ITC) and NMR techniques have been employed to characterize the interaction between a dicationic derivative of distamycin A (compound1) and the [d(TGGGGT)]4quadruplex. Additionally, to compare the binding behaviour of netropsin and compound1to the same target, a calometric study of the interaction between netropsin and [d(TGGGGT)]4has been performed. Experiments show that netropsin and compound1are able to bind to [d(TGGGGT)]4with good affinity and comparable thermodynamic profiles. In both cases the interactions are entropically driven processes with a small favourable enthalpic contribution. Interestingly, the structural modifications of compound1decrease the affinity of the ligand toward the duplex, enhancing the selectivity.

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G-Quadruplex-Based Drug Delivery Systems for Cancer Therapy

Pharmaceuticals ◽

10.3390/ph14070671 ◽

2021 ◽

Vol 14 (7) ◽

pp. 671

Author(s):

Jéssica Lopes-Nunes ◽

Paula Oliveira ◽

Carla Cruz

Keyword(s):

Drug Delivery ◽

Small Molecules ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Nano Particles ◽

Future Research ◽

High Affinity ◽

Dna And Rna ◽

G Quadruplex ◽

Gold Nano Particles

G-quadruplexes (G4s) are a class of nucleic acids (DNA and RNA) with single-stranded G-rich sequences. Owing to the selectivity of some G4s, they are emerging as targeting agents to overtake side effects of several potential anticancer drugs, and delivery systems of small molecules to malignant cells, through their high affinity or complementarity to specific targets. Moreover, different systems are being used to improve their potential, such as gold nano-particles or liposomes. Thus, the present review provides relevant data about the different studies with G4s as drug delivery systems and the challenges that must be overcome in the future research.

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Up- and downregulation of mature miR-1587 function by modulating its G-quadruplex structure and using small molecules

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2018.10.017 ◽

2019 ◽

Vol 121 ◽

pp. 127-134 ◽

Cited By ~ 5

Author(s):

Fangyuan Li ◽

Wei Tan ◽

Han Chen ◽

Jiang Zhou ◽

Ming Xu ◽

...

Keyword(s):

Small Molecules ◽

Quadruplex Structure ◽

G Quadruplex

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G-Quadruplex-Helicase Interactions and the Impact of Small Molecules

Biophysical Journal ◽

10.1016/j.bpj.2018.11.257 ◽

2019 ◽

Vol 116 (3) ◽

pp. 39a

Author(s):

Parastoo Maleki ◽

Hamza Balci

Keyword(s):

Small Molecules ◽

G Quadruplex ◽

The Impact

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N-methyl mesoporphyrin IX as a highly selective light-up probe for G-quadruplex DNA

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424619300179 ◽

2019 ◽

Vol 23 (11n12) ◽

pp. 1195-1215 ◽

Cited By ~ 5

Author(s):

Ariana Yett ◽

Linda Yingqi Lin ◽

Dana Beseiso ◽

Joanne Miao ◽

Liliya A. Yatsunyk

Keyword(s):

Optical Properties ◽

Small Molecules ◽

Genomic Stability ◽

Water Soluble ◽

Biological Processes ◽

Binding Properties ◽

Quadruplex Dna ◽

Dna Structures ◽

G Quadruplex ◽

High Fluorescence

[Formula: see text]-methyl mesoporphyrin IX (NMM) is a water-soluble, non-symmetric porphyrin with excellent optical properties and unparalleled selectivity for G-quadruplex (GQ) DNA. G-quadruplexes are non-canonical DNA structures formed by guanine-rich sequences. They are implicated in genomic stability, longevity, and cancer. The ability of NMM to selectively recognize GQ structures makes it a valuable scaffold for designing novel GQ binders. In this review, we survey the literature describing the GQ-binding properties of NMM as well as its wide utility in chemistry and biology. We start with the discovery of the GQ-binding properties of NMM and the development of NMM-binding aptamers. We then discuss the optical properties of NMM, focusing on the light-switch effect — high fluorescence of NMM induced upon its binding to GQ DNA. Additionally, we examine the affinity and selectivity of NMM for GQs, as well as its ability to stabilize GQ structures and favor parallel GQ conformations. Furthermore, a portion of the review is dedicated to the applications of NMM-GQ complexes as biosensors for heavy metals, small molecules ([Formula: see text] ATP and pesticides), DNA, and proteins. Finally and importantly, we discuss the utility of NMM as a probe to investigate the roles of GQs in biological processes.

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