Synthesis of polyhydroxylated pyrrolidinyl analogs of sugar nucleotides. Experimental and computational studies on their interactions with GalNAC‐T's
Merino, Pedro (Universidad de Zaragoza) ; Juste, Veronica ; Montesa, Alejandro (Universidad de Zaragoza) ; Pereira, Sandra ; Orta, Sara ; Pedrón, Manuel (Universidad de Zaragoza) ; Jiménez, Ana I. ; Martín-Santamaría, Sonsoles ; Hurtado-Guerrero, Ramón ; Delso, Ignacio ; Tejero, Tomás (Universidad de Zaragoza)
Resumen: Direct coupling between polyhydroxylated pyrrolidinyl β-amino phosphonates and uridine monophosphate (UMP) yields polyhydroxylated pyrrolidinyl analogs of sugar nucleotides suitable inhibitors of N-acetyl-galactosyltransferases. β-Amino phosphonates have been synthesized in an enantiomerically pure form through the nucleophilic addition of a phosphonate to polyhydroxylated cyclic nitrones. The reaction has been studied in detail and excellent diastereoselectivities are obtained in agreement with a stereochemical model well supported by density functional theory calculations. Binding of the nucleotide analogs with N-acetylgalactosyltransferases GalNAc-T2, GalNAc-T14, and GalNAc-T16 has been studied both experimentally and computationally through molecular dynamics simulations. Saturation transfer difference nuclear magnetic resonance experiments and measurement of Kd values have been used to validate the binding model at the active site. These studies provide important information of the role of the pyrophosphate and pyrrolidinyl moieties on the observed affinity.
Idioma: Inglés
DOI: 10.1002/cbic.202500955
Año: 2026
Publicado en: ChemBioChem 27, 7 (2026), [14 pp.]
ISSN: 1439-4227
Tipo y forma: Article (Published version)
Área (Departamento): Área Química Orgánica (Dpto. Química Orgánica)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes.
Exportado de SIDERAL (2026-04-30-13:57:11)
Visitas y descargas
Idioma: Inglés
DOI: 10.1002/cbic.202500955
Año: 2026
Publicado en: ChemBioChem 27, 7 (2026), [14 pp.]
ISSN: 1439-4227
Tipo y forma: Article (Published version)
Área (Departamento): Área Química Orgánica (Dpto. Química Orgánica)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. Exportado de SIDERAL (2026-04-30-13:57:11)
Permalink:
Visitas y descargas
Este artículo se encuentra en las siguientes colecciones:
Articles > Artículos por área > Química Orgánica
Record created 2026-04-30, last modified 2026-04-30