Guanine quadruplexes are tetra-stranded nucleic acid structures currently raising significant interest in the context of the development of potential anticancer therapeutics with a new mode of action. They are composed of planar guanine tetrads, allowing a high-affinity targeting by using molecules with a large π surface. However, the extreme topological versatility of guanine quadruplexes impedes a straightforward targeting of particular preselected guanine-rich sequences. We report here a systematic study of a family of luminescent platinum(II) complexes devised to overcome this challenge. By attaching a pendant adenine or thymine nucleobase as a substituent to one of the ligands at the platinum center, an additional recognition site is introduced with the aim of modulating the affinity of the metal complex to different DNA sequences. By comparing different attached nucleobases and a series of linker moieties, first conclusions are drawn with respect to the scope of this approach.
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http://dx.doi.org/10.1002/cplu.202100135 | DOI Listing |
ACS Sens
January 2025
Center for Biomedical-photonics and Molecular Imaging, Advanced Diagnostic-Therapy Technology and Equipment Key Laboratory of Higher Education Institutions in Shaanxi Province, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710126, China.
Functional nucleic acids constitute a distinct category of nucleic acids that diverge from conventional nucleic acid amplification methodologies. They are capable of forming intricate hybrid structures through Hoogsteen and reverse Hoogsteen hydrogen bonding interactions between double-stranded and single-stranded DNA, thereby broadening the spectrum of DNA interactions. In recent years, functional DNA/RNA-based surface-enhanced Raman spectroscopy (SERS) has emerged as a potent platform capable of ultrasensitive and multiplexed detection of a variety of analytes of interest.
View Article and Find Full Text PDFSci Rep
January 2025
Institute of Biophysics, Czech Academy of Sciences , Královopolská 135, Brno, 612 65, Czech Republic.
Retroviruses are among the most extensively studied viral families, both historically and in contemporary research. They are primarily investigated in the fields of viral oncogenesis, reverse transcription mechanisms, and other infection-specific aspects. These include the integration of endogenous retroviruses (ERVs) into host genomes, a process widely utilized in genetic engineering, and the ongoing search for HIV/AIDS treatment.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Biomedical Sciences, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, MI, USA.
The "secondhit" pathway is responsible for biallelic inactivation of many tumor suppressors, where a pathogenic germline allele is joined by somatic mutation of the remaining functional allele. The mechanisms are unresolved, but the human PKD1 tumor suppressor is a good experimental model for identifying the molecular determinants. Inactivation of PKD1 results in autosomal dominant polycystic kidney disease, a very common disorder characterized by the accumulation of fluid-filled cysts and end-stage renal disease.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, Naples 80131, Italy.
Iron homeostasis is strictly related to numerous physiological pathways including cell cycle progression and cell growth. The newest anticancer strategies focus on either depleting the cells with a suitable chelator or increasing their loading by administering iron complexes to induce ferroptosis. Iron depletion inhibits cell proliferation, while iron overload induces the damage of guanine nucleobases in G-quadruplex structures via ROS generation, leading to genome instability.
View Article and Find Full Text PDFJ Phys Chem A
December 2024
PDC Center for High Performance Computing, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden.
An automatic code generated C++/HIP/CUDA implementation of the (auxiliary) Fock, or Kohn-Sham, matrix construction for execution in GPU-accelerated hardware environments is presented. The module is developed as part of the quantum chemistry software package VeloxChem, employing localized Gaussian atomic orbitals. The performance and scaling characteristics are analyzed in view of the specific requirements for self-consistent field optimization and response theory calculations.
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