The interactions of G-quadruplex DNA with two oxidation products of papaverine, 6a,12a-diazadibenzo-[a,g]fluorenylium derivative (1) and 2,3,9,10-tetramethoxy-12-oxo-12H-indolo[2,1-a]isoquinolinium cation (2) were investigated. Their activity against telomerase was assessed using the conventional telomeric repeat amplification protocol (TRAP) assay. Effect of TRAP buffer and oligonucleotide length on the DNA-binding affinity of 1 and 2 were also studied. Three quadruplex-forming oligonucleotides with human telomeric sequence: dG(3)(T(2)AG(3))(3) (htel21), dAG(3)(T(2)AG(3))(3) (htel22), and d(T(2)AG(3))(4) (htel24) were used in these investigations. Both ligands were capable of interacting with G4 DNA with binding stoichiometry indicating that two ligand molecules bind to G-quadruplex, which agrees with the binding model of end-stacking on terminal G-tetrads. Circular dichroism spectra revealed that preferences of quadruplex-forming oligonucleotide to adopt a particular topological structure may be also affected by the external ligand that binds to quadruplex. Telomerase activity was suppressed at very low ligand 1 and ligand 2 concentrations with an appreciable selectivity comparing with inhibition of Taq polymerase.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ijbiomac.2007.07.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Deciphering Binding Potential of Naphthalimide-Coumarin Conjugate with c-MYC G-Quadruplex for Developing Anticancer Agents: A Spectroscopic and Molecular Modeling Approach.
ACS Appl Bio Mater
January 2025
Department of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology, Patiala-147001, India.
It has been well accumulated that G-quadruplex (G4-DNA) has great anticancer relevance, and various heterocyclic moieties have been synthesized and examined as potent G4-DNA binders with promising anticancer activity. Here, we have synthesized a series of naphthalimide-triazole-coumarin conjugates by substituting various amines and further examine their anticancer activity against 60 human cancer cell lines at 10 μM. One and five dose concentration results reveal low values of MG-MID GI for compounds including (3.
View Article and Find Full Text PDFAtomistic Insights Into Interaction of Doxorubicin With DNA: From Duplex to Nucleosome.
J Comput Chem
January 2025
Regional Center of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute (CATRIN), Palacký University Olomouc, Olomouc, Czech Republic.
Doxorubicin (DOX) is a widely used chemotherapeutic agent known for intercalating into DNA. However, the exact modes of DOX interactions with various DNA structures remain unclear. Using molecular dynamics (MD) simulations, we explored DOX interactions with DNA duplexes (dsDNA), G-quadruplex, and nucleosome.
View Article and Find Full Text PDFPreferential Binding of a Long-Arm Porphyrin Ligand to Higher Order G-Quadruplex under Crowding Conditions.
J 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 PDFSpermine Enhances the Peroxidase Activities of Multimeric Antiparallel G-quadruplex DNAzymes.
Biosensors (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 PDFAdvancing DNA Structural Analysis: A SERS Approach Free from Citrate Interference Combined with Machine Learning.
J 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 PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!