Browsing by Author "Dinamarca-Villarroel, Luis"

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    A comparative study on the cucurbit[7]uril-based indicator displacement assay for methyl Viologen. A theoretical and experimental perspective
    Pavez Guerrero, Paulina; Fierro Huerta, Angelica Maria; Rojas Guerrero, Mabel Natalia; Garcia-Rio, Luis; Dinamarca-Villarroel, Luis; Fuentealba Patino, Denis Alberto; Droguett Muñoz, Kevin Arturo; Santos Blanco, José Guillermo; Aliaga Miranda, Margarita Elly
    One colorimetric and one fluorescent-indicator displacement assay (IDA) were studied to assess their interaction with methyl viologen (MV), an herbicide commercially known as paraquat. The host–guest complexes formed by cucurbit[7]uril (CB[7]) and the 4-nitroaniline (NA) or Berberine (Be) dyes function as colorimetric- and fluorescent-IDA for MV, respectively. The CB[7]@NA and CB[7]@Be complexes were characterized by UV–vis, fluorescence spectroscopy, and dynamic simulations. Isothermal titration calorimetry (ITC) experiments and dynamic simulations were employed to obtain thermodynamic data for the formation of the 1:1 inclusion complexes. Finally, NA is proposed as a reference colorimetric dye for determining CB[7]-binding affinities using competitive host–guest titrations, and the fluorescent-IDA as the best assay proposed, as it exhibits a high binding constant, a good detection limit of 2.7 × 10−6 mol L-1, good linearity in the range from 4 × 10−6 mol L-1 to 3.5 × 10−5 mol L-1, in aqueous solution.
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    Collective and Coordinated Conformational Changes Determine Agonism or Antagonism at the Human Trace Amine-Associated Receptor 1
    (2023) Robles, Agustin I.; Dinamarca-Villarroel, Luis; Torres, Gonzalo E.; Fierro, Angelica
    The human trace amine-associated receptor (hTAAR1), a G protein-coupled receptor, has been postulated as a new target in the treatment of neuropsychiatric conditions. The mechanism associated with activation or inactivation by agonists or antagonists in hTAAR1 and other GPCRs has not yet been fully elucidated. In this study, we combined computational methods including homology modeling, docking, and molecular dynamic simulations to reveal novel conformational changes associated with agonist and antagonist interactions in hTAAR1. Our findings suggest a differential cascade of coordinated movements based on the presence of either an agonist or antagonist and primarily involving the second extracellular loop, transmembrane domain 5, and the third intracellular domains of hTAAR1. Our study provides an opportunity to predict the effects on new ligands with agonistic or antagonistic activity at hTAAR1 based on the reported conformational changes.
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    Linear relationship between emission quantum yield and Stokes shift in 3-styryl aza-coumarin based dyes in the presence of cyclodextrins
    (2023) Alcazar, Jackson J.; Garcia-Rio, Luis; Robles, Agustin I.; Dinamarca-Villarroel, Luis; Fierro, Angelica; Santos, Jose G.; Aliaga, Margarita E.
    The effect of the cyclodextrins inclusion on the Stokes shifts and emission quantum yield of three 3-styryl aza-coumarin dyes (SACs) was experimentally and theoretically studied. Preliminary results show a rela-tionship between the emission quantum yield and the calculated binding constants. Supramolecular inclusion was supported by changes in the fluorescence spectra, high-resolution mass spectrometry and molecular dynamics studies. 2,6-di-O-methyl-b-cyclodextrin (DM -b-CD) presented higher binding constants than b-cyclodextrin (b-CD), along with up to a 6-fold increase in emission quantum yield for the SACs. Additionally, a linear negative correlation was obtained between the Stokes shift and the emis-sion quantum yield. This linear and empirical relationship was explained by the action of a unique intramolecular rotation and charge transfer phenomenon in the dyes, which was modulated by cyclodex-trins, and supported by calculations based on density functional theory.(c) 2023 Elsevier B.V. All rights reserved.