170924 20260430151735.0 doi 10.1002/cbic.202500955 sideral 148989 ART-2026-148989 eng Merino, Pedro Universidad de Zaragoza (orcid)0000-0002-2202-3460 Synthesis of polyhydroxylated pyrrolidinyl analogs of sugar nucleotides. Experimental and computational studies on their interactions with GalNAC‐T's 2026 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. Access copy available to the general public Unrestricted info:eu-repo/semantics/openAccess by-nc https://creativecommons.org/licenses/by-nc/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Juste, Veronica (orcid)0000-0001-7200-7031 Montesa, Alejandro Universidad de Zaragoza Pereira, Sandra Orta, Sara (orcid)0000-0003-2952-7984 Pedrón, Manuel Universidad de Zaragoza (orcid)0000-0003-4249-6748 Jiménez, Ana I. (orcid)0000-0001-8057-4861 Martín-Santamaría, Sonsoles Hurtado-Guerrero, Ramón (orcid)0000-0002-3122-9401 Delso, Ignacio (orcid)0000-0001-8355-2289 Tejero, Tomás Universidad de Zaragoza (orcid)0000-0003-3433-6701 2013 765 Universidad de Zaragoza Dpto. Química Orgánica Área Química Orgánica 27, 7 (2026), [14 pp.] CHEMBIOCHEM ChemBioChem 1439-4227 1475343 http://zaguan.unizar.es/record/170924/files/texto_completo.pdf Versión publicada 2508322 http://zaguan.unizar.es/record/170924/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:170924 articulos driver 2026-04-30-13:57:11 ARTICLE