A topoisomerase I DNA unwinding assay has been used to determine the relative DNA-binding affinities of a model pair of homologous naphthalene diimides. Binding affinity data were corroborated using calorimetric (ITC) and spectrophotometric (titration and T(m)) studies, with substituent size playing a significant role in binding. The assay was also used to investigate the mode of binding adopted by several known DNA-binding agents, including SYBR Green and PicoGreen. Some of the compounds exhibited unexpected binding modes.
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http://dx.doi.org/10.1016/j.bmcl.2006.11.038 | DOI Listing |
ACS Med Chem Lett
January 2025
Discovery Biology, PMV Pharmaceuticals, Inc., 400 Alexander Park Drive, Suite 301, Princeton, New Jersey 08540, United States.
p53 is a potent transcription factor that is crucial in regulating cellular responses to stress. Mutations in the gene are found in >50% of human cancers, predominantly occurring in the DNA-binding domain (amino acids 94-292). The Y220C mutation accounts for 1.
View Article and Find Full Text PDFJ Phys Chem B
January 2025
Intermolecular Interaction Laboratory, Department of Bioinorganic Chemistry, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
This study extends previous research, particularly focusing on patented scientific objects No. ID: PL 240 353 B1, investigating the physicochemical properties of the methyl 3-azido- and 3-amino-2,3-dideoxysaccharides with a nucleoside scaffold similar to 3'-azidothymidine (AZT). The study utilizes multiwavelength spectrophotometric and potentiometric methods to evaluate the ionization of the saccharide units in aqueous solutions.
View Article and Find Full Text PDFArch Pharm (Weinheim)
January 2025
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch Russian Academy of Sciences, Novosibirsk, Russian Federation.
Tyrosyl DNA phosphodiesterases 1 and 2 (TDP1 and TDP2), which are enzymes involved in the repair of DNA, are regarded as promising targets for the development of new anticancer drugs. In this study, a series of imidazolidine-2,4-diones, 2,4,5-triones, and 2-thioxoimidazolidine-4,5-diones based on dehydroabietylamine (DHAAm) were synthesized. The inhibitory activity of the new compounds against TDP1 and TDP2, as well as their cytotoxic characteristics, were evaluated.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 24 Kashirskoe Shosse, 115522 Moscow, Russia.
Previously we discovered that among 15 DNA-binding plant secondary metabolites (PSMs) possessing anticancer activity, 11 compounds cause depletion of the chromatin-bound linker histones H1.2 and/or H1.4.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland.
Copper compounds with artificial metallo-nuclease (AMN) activity are mechanistically unique compared to established metallodrugs. Here, we describe the development of a new dinuclear copper AMN, Cu2-BPL-C6 (BPL-C6 = bis-1,10-phenanthroline-carbon-6), prepared using click chemistry that demonstrates site-specific DNA recognition with low micromolar cleavage activity. The BPL-C6 ligand was designed to force two redox-active copper centres-central for enhancing AMN activity-to bind DNA, via two phenanthroline ligands separated by an aliphatic linker.
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