G-quadruplex structures in nucleic acids have become attractive targets of study because their distinct structural forms may have diverse biological functions. Here, we preliminary investigated the structure and thermodynamics of G-quadruplexes of RNAs and corresponding DNAs of the same sequence by CD, UV and PAGE. Structural analysis demonstrated that the RNA sequences folded into a parallel-stranded G-quadruplex independently of surrounding conditions with different cations (K(+) and Na(+)) under both dilute and molecular crowding conditions. In contrast, G-quadruplexes of their corresponding DNA sequences showed structural polymorphism depending on the surrounding conditions. Moreover, it was demonstrated that parallel G-quadruplexes of the RNA sequences were more stable than either parallel or antiparallel G-quadruplexes of the same DNA sequences. These results allow us to propose a single, robust RNA G-quadruplex structure that exists under various conditions.
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http://dx.doi.org/10.1016/j.jbiotec.2010.07.026 | DOI Listing |
Int J Mol Sci
December 2024
Department of Pharmacy, University of Naples Federico II, 80131 Napoli, Italy.
Thrombin binding aptamer (TBA) is one of the best-known G-quadruplex (G4)-forming aptamers that efficiently binds to thrombin, resulting in anticoagulant effects. TBA also possesses promising antiproliferative properties. As with most therapeutic oligonucleotides, chemical modifications are critical for therapeutic applications, particularly to improve thermodynamic stability, resistance in biological environment, and target affinity.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Nation-Regional Engineering Lab for Synthetic Biology of Medicine, International Cancer Center, School of Pharmacy, Shenzhen University Medical School, Shenzhen 518060, China. Electronic address:
Lung cancer is the malignant tumor with the highest morbidity and mortality rate worldwide, of which non-small cell lung cancer (NSCLC) accounts for approximately 85%. KRAS mutations are one of the significant mechanisms underlying the occurrence, development, immune escape, and chemotherapy resistance of NSCLC. Two KRAS inhibitors are approved by FDA for the treatment of NSCLC in the past three years.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy. Electronic address:
Breast cancer, a leading cause of cancer-related mortality in women, is characterized by genomic instability and aberrant gene expression, often influenced by noncanonical nucleic acid structures such as G-quadruplexes (G4s). These structures, commonly found in the promoter regions and 5'-untranslated RNA sequences of several oncogenes, play crucial roles in regulating transcription and translation. Stabilizing these G4 structures offers a promising therapeutic strategy for targeting key oncogenic pathways.
View Article and Find Full Text PDFMolecules
December 2024
Dipartimento di Scienze della Salute, Università "Magna Græcia" di Catanzaro, Viale Europa, 88100 Catanzaro, Italy.
G-quadruplexes (G4s) are distinctive four-stranded nucleic acid structures formed by guanine-rich sequences, making them attractive targets for drug repurposing efforts. Modulating their stability and function holds promise for treating diseases like cancer. To identify potential drug candidates capable of interacting with these complex DNA formations, docking studies and molecular dynamics (MDs) simulations were conducted.
View Article and Find Full Text PDFCrit Rev Biotechnol
January 2025
Centre of Excellence in Epigenetics, Department of Life Sciences, Shiv Nadar Institution of Eminence, Gautam Buddha Nagar, India.
G-quadruplex structures (GQSes) are the intricate molecular knots or marvels that play diverse roles in various cellular processes, such as replication, transcription, and translation, which regulate gene expression. Even though GQSes can be found throughout the genome, they are more prevalent in certain genomic regions like promoters and 5'-UTRs. This review discusses the functionality of GQSes across various regions of the genome and draws attention to the intriguing world of DNA and RNA GQSes.
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