3,4-Dideoxy-3,3,4,4-tetrafluoro- and 4-OH epimeric 3-deoxy-3,3-difluoro-α-GalCer analogues: Synthesis and biological evaluation on human iNKT cells stimulation - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2019

3,4-Dideoxy-3,3,4,4-tetrafluoro- and 4-OH epimeric 3-deoxy-3,3-difluoro-α-GalCer analogues: Synthesis and biological evaluation on human iNKT cells stimulation

Bruno Linclau

Résumé

iNKT cells recognize CD1d/α-galactosylceramide (α-GalCer) complexes via their invariant TCR receptor and stimulate the immune response. Many α-GalCer analogues have been investigated to interrogate this interaction. Following our previous work related to the modification of the hydrogen bond network between α-GalCer and CD1d, we have now focused our attention on the synthesis of 3-deoxy-3,3-difluoro- and 3,4-dideoxy-3,3,4,4-tetrafluoro-α-GalCer analogues, and studied their ability to stimulate human iNKT cells. In each case, deoxygenation at the indicated positions was accompanied by difluoro introduction in order to evaluate the resulting electronic effect on the stability of the ternary CD1d/Galcer/TCR complex which has been rationalized by modeling study. With deoxy-difluorination at the 3-position, the two epimeric 4-OH analogues were investigated to establish their capacity to compensate for the lack of the hydrogen bond donating group at the 3-position. The 3,4-dideoxytetrafluoro analogue was of interest to highlight the amide NH-bond hydrogen bond properties.
Fichier principal
Vignette du fichier
S0223523419304878.pdf (944.36 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03086847 , version 1 (25-10-2021)

Licence

Paternité - Pas d'utilisation commerciale

Identifiants

Citer

Samuel Golten, Allan Patinec, Katy Akoumany, Jézabel Rocher, Jérôme Graton, et al.. 3,4-Dideoxy-3,3,4,4-tetrafluoro- and 4-OH epimeric 3-deoxy-3,3-difluoro-α-GalCer analogues: Synthesis and biological evaluation on human iNKT cells stimulation. European Journal of Medicinal Chemistry, 2019, 178, pp.195-213. ⟨10.1016/j.ejmech.2019.05.069⟩. ⟨hal-03086847⟩
224 Consultations
162 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More