Isothermal titration calorimetry and molecular modeling study of the complex formation of daclatasvir by γ-cyclodextrin and trimethyl-β-cyclodextrin - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Carbohydrate Polymers Année : 2023

Isothermal titration calorimetry and molecular modeling study of the complex formation of daclatasvir by γ-cyclodextrin and trimethyl-β-cyclodextrin

Résumé

The complex formation between daclatasvir and γ-CD or heptakis(2,3,6-tri-O-methyl)-β-CD (TM-β-CD) was studied by isothermal titration calorimetry and molecular modeling. Both techniques supported the predominant formation of a 2:1 complex in case of γ-CD although a 1:1 complex may be formed to a much lower extent as well. In case of TM-β-CD the stoichiometry of the complex was exclusively 1:1. Complex formation with γ-CD did not require dissociation of the daclatasvir dimer, which is present in solution, and resulted in a complex with a binding constant of 1.67·107 M−2. In contrast, formation of the weak TM-β-CD complex (K = 371 M−1) required dissociation of the daclatasvir dimer. This is in line with the observation that the complex formation in case of γ-CD is enthalpy-driven, while the process is entropy-driven in case of TM-β-CD. It is concluded that the plateau observed in capillary electrophoresis is primarily based on the slow dissociation of the daclatasvir-CD complexes caused by steric constrains due to the folded terminal amino acid moieties of daclatasvir exerting a clip effect. In case γ-CD the thermodynamic stability might contribute to the overall slow dissociation.

Dates et versions

hal-04320638 , version 1 (04-12-2023)

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Paola Peluso, David Landy, Lamia Nakhle, Roberto Dallocchio, Alessandro Dessì, et al.. Isothermal titration calorimetry and molecular modeling study of the complex formation of daclatasvir by γ-cyclodextrin and trimethyl-β-cyclodextrin. Carbohydrate Polymers, 2023, 313, pp.120870. ⟨10.1016/j.carbpol.2023.120870⟩. ⟨hal-04320638⟩
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