000170924 001__ 170924
000170924 005__ 20260430151735.0
000170924 0247_ $$2doi$$a10.1002/cbic.202500955
000170924 0248_ $$2sideral$$a148989
000170924 037__ $$aART-2026-148989
000170924 041__ $$aeng
000170924 100__ $$0(orcid)0000-0002-2202-3460$$aMerino, Pedro$$uUniversidad de Zaragoza
000170924 245__ $$aSynthesis of polyhydroxylated pyrrolidinyl analogs of sugar nucleotides. Experimental and computational studies on their interactions with GalNAC‐T's
000170924 260__ $$c2026
000170924 5060_ $$aAccess copy available to the general public$$fUnrestricted
000170924 5203_ $$aDirect 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.
000170924 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttps://creativecommons.org/licenses/by-nc/4.0/deed.es
000170924 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000170924 700__ $$0(orcid)0000-0001-7200-7031$$aJuste, Veronica
000170924 700__ $$aMontesa, Alejandro$$uUniversidad de Zaragoza
000170924 700__ $$aPereira, Sandra
000170924 700__ $$0(orcid)0000-0003-2952-7984$$aOrta, Sara
000170924 700__ $$0(orcid)0000-0003-4249-6748$$aPedrón, Manuel$$uUniversidad de Zaragoza
000170924 700__ $$0(orcid)0000-0001-8057-4861$$aJiménez, Ana I.
000170924 700__ $$aMartín-Santamaría, Sonsoles
000170924 700__ $$0(orcid)0000-0002-3122-9401$$aHurtado-Guerrero, Ramón
000170924 700__ $$0(orcid)0000-0001-8355-2289$$aDelso, Ignacio
000170924 700__ $$0(orcid)0000-0003-3433-6701$$aTejero, Tomás$$uUniversidad de Zaragoza
000170924 7102_ $$12013$$2765$$aUniversidad de Zaragoza$$bDpto. Química Orgánica$$cÁrea Química Orgánica
000170924 773__ $$g27, 7 (2026), [14 pp.]$$pCHEMBIOCHEM$$tChemBioChem$$x1439-4227
000170924 8564_ $$s1475343$$uhttps://zaguan.unizar.es/record/170924/files/texto_completo.pdf$$yVersión publicada
000170924 8564_ $$s2508322$$uhttps://zaguan.unizar.es/record/170924/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000170924 909CO $$ooai:zaguan.unizar.es:170924$$particulos$$pdriver
000170924 951__ $$a2026-04-30-13:57:11
000170924 980__ $$aARTICLE