Dinucleoside monophosphates containing AZT and 1-methyladenosine or 7-methylguanosine were synthesized and their in vitro anti-HIV activity was determined.
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Membrane-embedded CdaA is required for efficient synthesis of second messenger cyclic di-AMP.
Commun Biol
December 2024
Department of Biochemistry, Groningen Biomolecular Science and Biotechnology Institute, University of Groningen, Nijenborgh 3, Groningen, The Netherlands.
Cyclic di-adenylate monophosphate (cyclic di-AMP) is an important second messenger in microorganisms. Cyclic di-AMP regulates bacterial cell volume and turgor via control of potassium and compatible solute transport but is also involved in many other processes, including the activation of the metazoan innate immune response to bacterial infections. We compare the activity of full-length membrane-embedded CdaA, the enzyme that synthesizes cyclic di-AMP, with the water-soluble catalytic domain CdaA-DAC.
View Article and Find Full Text PDFBiofilm formation by is triggered by a drop in the levels of a cyclic dinucleotide.
Proc Natl Acad Sci U S A
December 2024
Department of Biochemistry, Brandeis University, Waltham, MA 02453.
The bacterial pathogen forms multicellular communities known as biofilms in which cells are held together by an extracellular matrix principally composed of repurposed cytoplasmic proteins and extracellular DNA. These biofilms assemble during infections or under laboratory conditions by growth on medium containing glucose, but the intracellular signal for biofilm formation and its downstream targets were unknown. Here, we present evidence that biofilm formation is triggered by a drop in the levels of the second messenger cyclic-di-AMP.
View Article and Find Full Text PDFC-di-AMP accumulation disrupts glutathione metabolism in .
Infect Immun
December 2024
Food Science Department, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Article Synopsis
- C-di-AMP is crucial for bacterial functions like stress response, maintaining cell wall integrity, and virulence, but its precise molecular mechanisms are not fully understood.
- A mutant strain lacking c-di-AMP phosphodiesterases (ΔPDE) shows reduced virulence in a mouse infection model and is impaired in expressing virulence genes that are typically activated by reduced glutathione (GSH).
- The ΔPDE strain also has lower GSH levels and is less able to absorb GSH, suggesting that the buildup of c-di-AMP hinders GSH metabolism, which might explain its decreased virulence despite some restoration of gene expression through a modified PrfA protein.
Intranasal immunization with CPAF combined with ADU-S100 induces an effector CD4 T cell response and reduces bacterial burden following intravaginal infection with Chlamydia muridarum.
Vaccine
January 2025
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Chlamydia trachomatis (Ct) is the most common bacterial sexually transmitted infection globally, and a vaccine is urgently needed to stop transmission and disease. Chlamydial Protease Activity Factor (CPAF) is an immunoprevalent and immunodominant antigen for CD4 T cells and B cells, which makes it a strong vaccine candidate. Due to the tolerogenic nature of the female genital tract (FGT) and its lack of secondary lymphoid tissue, effective induction of protective cell-mediated immunity will likely require potent and safe mucosal adjuvants.
View Article and Find Full Text PDFOptimization of a high throughput screening platform to identify inhibitors of asymmetric diadenosine polyphosphatases.
Anal Biochem
February 2025
School of Chemistry and Materials Science, Rochester Institute of Technology, United States. Electronic address:
When stressed, cells synthesize di-adenosine polyphosphates (ApA), and cellular organisms also express proteins that degrade these compounds to release ATP. Most of these proteins are members of the nudix hydrolase superfamily, and several are involved in bacterial pathogenesis, neurodevelopment, and cancer. The goal of this project is to assist in the discovery of inhibitors of these enzymes that could be used to study ApA function and the cellular role of these nudix enzymes.
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