Publications by authors named "Kofi S Yeboah"
The protein kinases CLK and ROCK play key roles in cell growth and migration, respectively, and are potential anticancer targets. ROCK inhibitors have been approved by the FDA for various diseases and CLK inhibitors are currently being trialed in the clinic as anticancer agents. Compounds with polypharmacology are desired, especially in oncology, due to the potential for high efficacy as well as addressing resistance issues.
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- Cyclic dinucleotides like cGAMP, c-di-GMP, and c-di-AMP are important second messengers in various organisms, creating a demand for efficient detection methods in biological studies.
- In response to the need for simpler assays, the authors develop a new fluorescent polarization (FP) assay using fluorescein-labeled c-di-GMP, which proves to be the most effective for binding to STING, a key protein in cellular signaling.
- This universal probe can be displaced by other cyclic dinucleotides, allowing for monitoring of all three compounds, and is validated through HPLC analysis.
Article Synopsis
- Host cells recognize cytosolic double-stranded DNA and cyclic dinucleotides through the STING molecule, triggering an innate immune response that produces Type I interferons and proinflammatory cytokines.
- The review explores how bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway may contribute to the development and immune regulation of periodontal disease.
- It also discusses potential activators and inhibitors of the STING pathway, highlighting their promise in treating periodontitis and suggesting insights for future research into immune therapies.
Immune cells sense bacteria-derived c-di-GMP and c-di-AMP as well as host-derived cGAMP, which is synthesized by cGAS upon binding to the pathogen's DNA, to mount an immunological response (cytokine production) via the STING-TBK1 pathway. Successful pathogens, such as and group B streptococcus, harbor phosphodiesterases (PDEs) that can cleave bacterial c-di-AMP as well as host-derived cGAMP to blunt the host's response to infection. Selective inhibitors of bacterial cyclic dinucleotide (CDN) PDEs are needed as tool compounds to study the role(s) of CDN PDEs during infection and they could also become bona fide antivirulence compounds, but there is a paucity of such compounds.
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