We synthesized a miR-122 antimiR library in which drug-like fragments were site-specifically introduced to short 2'-O-methyl-RNAs. At some sites selected fragments elevated cellular antimiR activity to that of an unmodified 23mer antimiR, whereas at others the same fragments abolished activity. The potency of the antimiRs correlated with uptake into miRISC.
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http://dx.doi.org/10.1039/c5cc07478a | DOI Listing |
ACS Cent Sci
January 2025
Department of Chemistry, Technical University of Denmark, 2800, Kongens Lyngby, Denmark.
Sterol transport proteins mediate intracellular sterol transport, organelle contact sites, and lipid metabolism. Despite their importance, the similarities in their sterol-binding domains have made the identification of selective modulators difficult. Herein we report a combination of different compound library synthesis strategies to prepare a cholic acid-inspired compound collection for the identification of potent and selective inhibitors of sterol transport proteins.
View Article and Find Full Text PDFChem Sci
December 2024
ByteDance Research Bellevue Washington 98004 USA
A force field is a critical component in molecular dynamics simulations for computational drug discovery. It must achieve high accuracy within the constraints of molecular mechanics' (MM) limited functional forms, which offers high computational efficiency. With the rapid expansion of synthetically accessible chemical space, traditional look-up table approaches face significant challenges.
View Article and Find Full Text PDFBMC Chem
January 2025
LAQV@REQUIMTE/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, 4169-007, Portugal.
Mood disorders affect the daily lives of millions of people worldwide. The search for more efficient therapies for mood disorders remains an active field of research. In silico approaches can accelerate the search for inhibitors against protein targets related to mood disorders.
View Article and Find Full Text PDFChem Biodivers
December 2024
Faculty of Medicine, Department of Chemistry, University of Niš, Niš, Serbia.
The thieno[2,3-d]pyrimidine fragment is in the structure of many drug-like candidate derivatives with a wide range of biological activities. However, very few dipeptidyl peptidase-4 (DPP-4) inhibitors with this building block are currently known. Here, the selection of a novel DPP-4 inhibitor based on the thienopyrimidine scaffold is reported.
View Article and Find Full Text PDFACS Chem Neurosci
January 2025
Department of Chemistry, Center for Research and Advanced Studies (Cinvestav), Mexico City 07360, Mexico.
Alzheimer's disease (AD) is the most common form of dementia worldwide. AD brains are characterized by the accumulation of amyloid-β peptides (Aβ) that bind Cu and have been associated with several neurotoxic mechanisms. Although the use of copper chelators to prevent the formation of Cu-Aβ complexes has been proposed as a therapeutic strategy, recent studies show that copper is an important neuromodulator that is essential for a neuroprotective mechanism mediated by Cu binding to the cellular prion protein (PrP).
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