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Reconfigurable structures engineered through DNA hybridization and self-assembly offer both structural and dynamic applications in nanotechnology. Here, we have demonstrated that strand displacement of triplex-forming oligonucleotides (TFOs) can be translated to a robust macroscopic DNA crystal by coloring the crystals with covalently attached fluorescent dyes. We show that three different types of triplex strand displacement are feasible within the DNA crystals and the bound TFOs can be removed and/or replaced by (a) changing the pH from 5 to 7, (b) the addition of the Watson-Crick complement to a TFO containing a short toehold, and (c) the addition of a longer TFO that uses the duplex edge as a toehold. We have also proved by X-ray diffraction that the structure of the crystals remains as designed in the presence of the TFOs.
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http://dx.doi.org/10.1021/jacs.2c12667 | DOI Listing |
RSC Chem Biol
July 2025
Institute for Pharmaceutical Chemistry, Johann Wolfgang Goethe-University Max-von-Laue-Str. 9 D-60438 Frankfurt am Main Germany
Herein we present the rapid development of LH168, a potent and highly selective chemical probe for WDR5, streamlined by utilizing a DEL-ML (DNA encoded library-machine learning) hit as the chemical starting point. LH168 was comprehensively characterized in bioassays and demonstrated potent target engagement at the WIN-site pocket of WDR5, with an EC of approximately 10 nM, a long residence time, and exceptional proteome-wide selectivity for WDR5. In addition, we present the X-ray co-crystal structure and provide insights into the structure-activity relationships (SAR).
View Article and Find Full Text PDFPLoS One
September 2025
Department of Urology, Kanazawa Medical University, Kahoku, Ishikawa, Japan.
Calcium oxalate (CaOx) stones are prevalent in urinary tract stone disease. While their formation can be induced in rats by administering ethylene glycol and vitamin D, the initial nucleation and formation processes are unclear. Here, we aimed to determine where CaOx crystals initially form, examine the associated histological and morphological changes, and clarify the genes whose expression varies at those sites and their function.
View Article and Find Full Text PDFEur J Med Chem
September 2025
Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland. Electronic address:
PARP10 is a potential drug target due to its overexpression in several cancer types and its roles in DNA repair mechanisms and tumorigenesis. In this study, we performed an optimization campaign on our earlier compounds based on a 2,3-dihydrophthalazine-1,4-dione scaffold which emerged with dual PARP10 and PARP15 inhibitory activity. The specific aim was to improve the potency and selectivity towards PARP10.
View Article and Find Full Text PDFCell Rep
September 2025
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Pôle de Recherches Sino-Français en Science du Vivant et Gé
RNA helicase DDX3X is generally implicated in inflammasome activation and anti-viral responses. We characterize the common features of scattered DDX3X mutations in lymphoid cancers using molecular dynamics simulation and crystallization, thereby demonstrating their crucial role in Epstein-Barr virus (EBV) lytic gene-driven oncogenic processes. The DDX3X mutation is significantly related to impaired stimulator of interferon genes (STING)/ interferon regulatory factor 7 (IRF-7)/interferon (IFN)-α/β-mediated innate immunity, overexpression of EBV lytic gene BNLF2b, and increased formation of R-loops.
View Article and Find Full Text PDFDrug Dev Res
September 2025
Cancer Biology Department, Pharmacology Unit, National Cancer Institute (NCI), Cairo University, Cairo, Egypt.
Herein, and based on the pharmacophoric features of doxorubicin (Dox); 133 steroids were screened to assess their ability to act as TOP II inhibitors for the discovery of those with promising anticancer activity. The cytotoxic inhibitory concentration 50 (IC) of the investigated steroids was determined against H1299, CaCo2, MDA-MB-468, and FaDu cancer cell lines and compared to Dox. Fluticasone propionate and fusidic acid exhibited the most potent antiproliferative effect against the MDA-MB-468 with IC values of 10.
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