Publications by authors named "A Villarroel"
Identification of Riluzole derivatives as novel calmodulin inhibitors with neuroprotective activity by a joint synthesis, biosensor, and computational guided strategy.
Biomed Pharmacother
May 2024
The development of new molecules for the treatment of calmodulin related cardiovascular or neurodegenerative diseases is an interesting goal. In this work, we introduce a novel strategy with four main steps: (1) chemical synthesis of target molecules, (2) Förster Resonance Energy Transfer (FRET) biosensor development and in vitro biological assay of new derivatives, (3) Cheminformatics models development and in vivo activity prediction, and (4) Docking studies. This strategy is illustrated with a case study.
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- * Most proteins don’t naturally fluoresce; however, proteins can be modified with fluorescent markers, with dansyl chloride (DNSC) recognized as a reliable option for such modifications.
- * The use of dansylated-calmodulin (D-CaM) allows for effective monitoring of protein and peptide interactions, providing insights into ligand affinity and the role of calcium in these processes.
Article Synopsis
- Despite advancements in genomic data and analysis, predicting disease severity is still challenging without clinical descriptors.
- The study focuses on the K7.2 potassium channel gene linked to epilepsy and developmental delays, introducing a new machine learning approach that combines genomic data with a Variant Frequency Index (VFI).
- The resulting ensemble model, MLe-KCNQ2, demonstrates high accuracy in classifying variants and offers valuable insights for clinical counseling, enhancing decision making for KCNQ2-related pathologies.
Neuronal K7 channels, important regulators of cell excitability, are among the most sensitive proteins to reactive oxygen species. The S2S3 linker of the voltage sensor was reported as a site-mediating redox modulation of the channels. Recent structural insights reveal potential interactions between this linker and the Ca-binding loop of the third EF-hand of calmodulin (CaM), which embraces an antiparallel fork formed by the C-terminal helices A and B, constituting the calcium responsive domain (CRD).
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