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Conditionally Activated ROS Generation by MMP2/9-Specific C-Based Fluorescence Probes.
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January 2025
Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 3, Zürich, 8093, Switzerland.
A C-coumarin conjugate, covalently connected via a matrix metalloproteinase (MMP2/9)-cleavable peptide linker (Pro-Leu-Gly-Val-Arg-Gly), is developed as a probe for both imaging and photodynamic treatment of MMP2/9-expressing malignant cells. In the synthesized probe, the coumarin fluorescence is completely suppressed intramolecularly by the C moiety, while an intensive fluorescence increase is observed in the presence of MMP2/9 dependent on cleavage of the peptide linker. The specificity of the probe to detect MMP2 is confirmed by control experiments resulting in no emission 1) with a control probe bearing a shuffled peptide (Val-Arg-Leu-Gly-Pro-Gly) or 2) in the presence of an MMP2 inhibitor (1,10-phenantheoline).
View Article and Find Full Text PDFRPRD1B's direct interaction with phosphorylated RNA polymerase II regulates polyadenylation of cell cycle genes and drives cancer progression.
RSC Chem Biol
January 2025
Department of Molecular Biosciences, University of Texas Austin Texas USA
RNA polymerase II (Pol II) regulates eukaryotic gene expression through dynamic phosphorylation of its C-terminal domain (CTD). Phosphorylation at Ser2 and Thr4 on the CTD is crucial for RNA 3' end processing and facilitating the recruitment of cleavage and termination factors. However, the transcriptional roles of most CTD-binding proteins remain poorly understood.
View Article and Find Full Text PDFTunable control of Cas12 activity promotes universal and fast one-pot nucleic acid detection.
Nat Commun
January 2025
CAS Key Laboratory of Urban Pollutant Conversion, Department of Environmental Science and Engineering, University of Science and Technology of China, 230026, Hefei, China.
The CRISPR-based detection methods have been widely applied, yet they remain limited by the non-universal nature of one-pot diagnostic approaches. Here, we report a universal one-pot fluorescent method for the detection of epidemic pathogens, delivering results within 15-20 min. This method uses heparin sodium to precisely tunes the cis-cleavage capability of Cas12 via interference with the Cas12a-crRNA binding process, thereby generating significant fluorescence due to the accumulation of isothermal amplification products.
View Article and Find Full Text PDFThe leader proteinase of foot-and-mouth disease virus: Efficiency through exosites.
Virology
January 2025
Max Perutz Labs, Medical University of Vienna, Dept. of Medical Biochemistry, Dr. Bohr-Gasse 9/3, A-1030, Vienna, Austria. Electronic address:
Viruses were shown to encode proteinases in the 1970s. Initially, it was assumed that they would be only used for proteolytic processing of the viral proteins. Subsequent investigations showed that such proteinases could affect host metabolism to benefit viral replication.
View Article and Find Full Text PDFA high-resolution view of RNA endonuclease cleavage in Bacillus subtilis.
Nucleic Acids Res
January 2025
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
RNA endonucleases are the rate-limiting initiator of decay for many bacterial mRNAs. However, the positions of cleavage and their sequence determinants remain elusive even for the well-studied Bacillus subtilis. Here we present two complementary approaches-transcriptome-wide mapping of endoribonucleolytic activity and deep mutational scanning of RNA cleavage sites-that reveal distinct rules governing the specificity among B.
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