Binding of actinomycin D (ActD) to the seemingly single-stranded DNA (ssDNA) oligomer 5'-CCGTT3 GTGG-3' has been studied in solution using high-resolution nuclear magnetic resonance (NMR) techniques. A strong binding constant (8 x 10(6) M(-1)) and high quality NMR spectra have allowed us to determine the initial DNA structure using distance geometry as well as the final ActD-5'-CCGTT3 GTGG-3' complex structure using constrained molecular dynamics calculations. The DNA oligomer 5'-CCGTT3GTGG-3' in the complex forms a hairpin structure with tandem G.T mismatches at the stem region next to a loop of three stacked thymine bases pointing toward the major groove. Bipartite T2O-GH1 and T2O-G2NH2 hydrogen bonds were detected for the G.T mismatches that further stabilize this unusual DNA hairpin. The phenoxazone chromophore of ActD intercalates nicely between the tandem G.T mismatches in essentially one major orientation. Additional hydrophobic interactions between the ActD quinoid amino acid residues with the loop T5-T6-T7 backbone protons were also observed. The hydrophobic G-phenoxazone-G interaction in the ActD-5'-CCGTT3GTGG-3' complex is more robust than that of the classical ActD- 5'-CCGCT3GCGG-3' complex, consistent with the roughly 2-fold stronger binding of ActD to the 5'-CCGTT3GTGG-3' sequence than to its 5'-CCG CT3GCGG-3' counterpart. Stabilization by ActD of a hairpin containing non-canonical stem base pairs further strengthens the notion that ActD or other related compounds may serve as a sequence- specific ssDNA-binding agent that inhibits human immunodeficiency virus (HIV) and other retroviruses replicating through ssDNA intermediates.
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http://dx.doi.org/10.1093/nar/gkg353 | DOI Listing |
Diagn Pathol
January 2025
Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studničkova 2, Prague, 12800, Czech Republic.
Background: Juvenile granulosa cell tumor (JGCT) of the ovary is a rare tumor with distinct clinicopathological and hormonal features primarily affecting young women and children. We conducted a complex clinicopathological, immunohistochemical, and molecular analysis of five cases of JGCT.
Methods: The immunohistochemical examination was performed with 32 markers, including markers that have not been previously investigated.
ACS Appl Mater Interfaces
January 2025
Jihua Hengye Electronic Materials Co. Ltd., Foshan, Guangdong Province 528200, P. R. China.
Charge generation layers (CGLs) play crucial roles in determining the electroluminescence (EL) performance of tandem organic light-emitting diodes (OLEDs). However, acquiring negligible voltage drops across the CGL unit and high-efficiency multiplications remains challenging. Here, we propose barrier-free strategies to compose a high-performance p-i-n type CGL intermediate by introducing a Yb/HI-9 modification at the heterojunction and a novel n-dopant, Yb:1,3-bis(9-phenyl-1,10-phenanthrolin-2-yl)benzene (mdPPhen), as the n-CGL.
View Article and Find Full Text PDFMolecules
November 2024
Research Center of Nano Science and Technology, College of Sciences, Shanghai University, Shanghai 200444, China.
Metallic heterostructural nanocrystals (HNCs) hold immense potential in electrocatalytic carbon dioxide reduction reaction (CORR) owing to their abundant active sites and high intrinsic activity. However, a significant challenge still remains in achieving controlled nucleation and growth sites for HNCs on supports and comprehending the influence of the structure-activity relationship on electrocatalytic CORR performance. This work presents a photochemical self-assembly technique without the necessity for reducing agents or facet-specific capping agents.
View Article and Find Full Text PDFACS Appl Mater Interfaces
December 2024
Department of Materials Science and Engineering, University of Virginia, Charlottesville, Virginia 22904, United States.
The discovery of ferroelectricity in hafnia based thin films has catalyzed significant research focused on understanding the ferroelectric property origins and means to increase stability of the ferroelectric phase. Prior studies have revealed that biaxial tensile stress via an electrode "capping effect" is a suspected ferroelectric phase stabilization mechanism. This effect is commonly reported to stem from a coefficient of thermal expansion (CTE) incongruency between the hafnia and top electrode.
View Article and Find Full Text PDFDNA Repair (Amst)
December 2024
Section on Gene Structure and Disease, Laboratory of Cell and Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
The Repeat Expansion Diseases (REDs) are a large group of human genetic disorders that result from an increase in the number of repeats in a disease-specific tandem repeat or microsatellite. Emerging evidence suggests that the repeats trigger an error-prone form of DNA repair that causes the expansion mutation by exploiting a limitation in normal mismatch repair. Furthermore, while much remains to be understood about how the mutation causes pathology in different diseases in this group, there is evidence to suggest that some of the downstream consequences of repeat expansion trigger the DNA damage response in ways that contribute to disease pathology.
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