G-quadruplexes are noncanonical secondary structures formed in DNA sequences containing consecutive runs of guanines. It has been shown that the 3' G-rich single-stranded overhangs of human telomeres can form G-quadruplex structures, and the human telomeric DNA G-quadruplexes are considered attractive targets for anticancer drugs. G-quadruplex-interactive compounds have been shown to inhibit telomerase access as well as telomere capping. Nuclear magnetic resonance (NMR) spectroscopy is a powerful method in determining the G-quadruplex structures under physiologically relevant conditions. We present the NMR and biophysical methodology used in our research group for the study of G-quadruplex structures in physiologically relevant solution and their interactions with small-molecule compounds.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516791 | PMC |
http://dx.doi.org/10.1007/978-1-4939-6892-3_17 | DOI Listing |
Biomolecules
January 2025
Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1-2-1 Sengen, Tsukuba 305-0047, Japan.
Synthetic cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) are promising candidates for vaccine adjuvants, because they activate immune responses through the Toll-like receptor 9 (TLR9) pathway. However, unmodified CpG ODNs are quickly degraded by serum nucleases, and their negative charge hinders cellular uptake, limiting their clinical application. Our group previously reported that guanine-quadruplex (G4)-forming CpG ODNs exhibit enhanced stability and cellular uptake.
View Article and Find Full Text PDFJ Phys Chem B
January 2025
College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
Under conditions that are close to the real cellular environment, the human telomeric single-stranded overhang (∼200 nt) consisting of tens of TTAGGG repeats tends to form higher order structures of multiple G-quadruplex (G4) blocks. On account of the higher biological relevance of higher order G4 structures, ligand compounds binding to higher order G4 are significant for the drug design toward inhibiting telomerase activity. Here, we study the interaction between a cationic porphyrin derivative, 5,10,15,20-tetra{4-[2-(1-methyl-1-piperidinyl)propoxy]phenyl}porphyrin (T4), and a human telomeric G4-dimer (AG(TAG)) in the mimic intracellular molecularly crowded environment (PEG as a crowding agent) and K or Na solution (i.
View Article and Find Full Text PDFBiosensors (Basel)
January 2025
School of Pharmacy & Biomolecular Sciences, Faculty of Health, Innovation, Technology and Science, Liverpool John Moores University, Liverpool L3 3AF, UK.
G-quadruplex (G4) DNAzymes with peroxidase activities hold potential for applications in biosensing. While these nanozymes are easy to assemble, they are not as efficient as natural peroxidase enzymes. Several approaches are being used to better understand the structural basis of their reaction mechanisms, with a view to designing constructs with improved catalytic activities.
View Article and Find Full Text PDFJ Phys Chem Lett
January 2025
State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Research Center for Innovative Technology of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Heilongjiang 150081, PR China.
Surface-enhanced Raman spectroscopy (SERS) has become an indispensable tool for biomolecular analysis, yet the detection of DNA signals remains hindered by spectral interference from citrate ions, which overlap with key DNA features. This study introduces an innovative, ultrasensitive SERS platform utilizing thiol-modified silver nanoparticles (Ag@SDCNPs) that overcomes this challenge by eliminating citrate interference. This platform enables direct, interference-free detection and structural characterization of a wide range of DNA conformations, including single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), i-motif, hairpin, G-quadruplex, and triple-stranded DNA (tsDNA).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Max Perutz Labs, Vienna Biocenter Campus, Vienna 1030, Austria.
RNA G-quadruplexes (rG4s), the four-stranded structures formed by guanine-rich RNA sequences, are recognized by regions in RNA-binding proteins (RBPs) that are enriched in arginine-glycine repeats (RGG motifs). Importantly, arginine and glycine are encoded by guanine-rich codons, suggesting that some RGG motifs may both be encoded by and interact with rG4s in autogenous messenger RNAs (mRNAs). By analyzing transcriptome-wide rG4 datasets, we show that hundreds of RGG motifs in humans are at least partly encoded by rG4s, with an increased incidence for longer RGG motifs (~10 or more residues).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!