000079330 001__ 79330
000079330 005__ 20200117221632.0
000079330 0247_ $$2doi$$a10.1002/chem.201801083
000079330 0248_ $$2sideral$$a107206
000079330 037__ $$aART-2018-107206
000079330 041__ $$aeng
000079330 100__ $$0(orcid)0000-0002-2855-4801$$aGhirardello, M.
000079330 245__ $$aUDP-GlcNAc Analogues as Inhibitors of O-GlcNAc Transferase (OGT): Spectroscopic, Computational, and Biological Studies
000079330 260__ $$c2018
000079330 5060_ $$aAccess copy available to the general public$$fUnrestricted
000079330 5203_ $$aA series of glycomimetics of UDP-GlcNAc, in which the ß-phosphate has been replaced by either an alkyl chain or a triazolyl ring and the sugar moiety has been replaced by a pyrrolidine ring, has been synthesized by the application of different click-chemistry procedures. Their affinities for human O-GlcNAc transferase (hOGT) have been evaluated and studied both spectroscopically and computationally. The binding epitopes of the best ligands have been determined in solution by means of saturation transfer difference (STD) NMR spectroscopy. Experimental, spectroscopic, and computational results are in agreement, pointing out the essential role of the binding of ß-phosphate. We have found that the loss of interactions from the ß-phosphate can be counterbalanced by the presence of hydrophobic groups at a pyrroline ring acting as a surrogate of the carbohydrate unit. Two of the prepared glycomimetics show inhibition at a micromolar level.
000079330 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E10$$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/CTQ2016-76155-R
000079330 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000079330 590__ $$a5.16$$b2018
000079330 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b36 / 172 = 0.209$$c2018$$dQ1$$eT1
000079330 592__ $$a1.842$$b2018
000079330 593__ $$aCatalysis$$c2018$$dQ1
000079330 593__ $$aOrganic Chemistry$$c2018$$dQ1
000079330 593__ $$aChemistry (miscellaneous)$$c2018$$dQ1
000079330 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000079330 700__ $$aPerrone, D.
000079330 700__ $$aChinaglia, N.
000079330 700__ $$0(orcid)0000-0001-5427-5673$$aSádaba, D.
000079330 700__ $$0(orcid)0000-0001-8355-2289$$aDelso, I.$$uUniversidad de Zaragoza
000079330 700__ $$0(orcid)0000-0003-3433-6701$$aTejero, T.$$uUniversidad de Zaragoza
000079330 700__ $$aMarchesi, E.
000079330 700__ $$aFogagnolo, M.
000079330 700__ $$aRafie, K.
000079330 700__ $$avan Aalten, D.M.F.
000079330 700__ $$0(orcid)0000-0002-2202-3460$$aMerino, P.$$uUniversidad de Zaragoza
000079330 7102_ $$12013$$2765$$aUniversidad de Zaragoza$$bDpto. Química Orgánica$$cÁrea Química Orgánica
000079330 773__ $$g24, 28 (2018), 7264-7272$$pChemistry (Weinh.)$$tChemistry - A European Journal$$x0947-6539
000079330 8564_ $$s920167$$uhttps://zaguan.unizar.es/record/79330/files/texto_completo.pdf$$yPostprint
000079330 8564_ $$s21180$$uhttps://zaguan.unizar.es/record/79330/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000079330 909CO $$ooai:zaguan.unizar.es:79330$$particulos$$pdriver
000079330 951__ $$a2020-01-17-22:00:34
000079330 980__ $$aARTICLE