000089679 001__ 89679
000089679 005__ 20210902121713.0
000089679 0247_ $$2doi$$a10.1039/c9sc06334j
000089679 0248_ $$2sideral$$a117802
000089679 037__ $$aART-2020-117802
000089679 041__ $$aeng
000089679 100__ $$aBermejo, I.A.
000089679 245__ $$aSynthesis, conformational analysis and In vivo assays of an anti-cancer vaccine that features an unnatural antigen based on an sp2-iminosugar fragment
000089679 260__ $$c2020
000089679 5060_ $$aAccess copy available to the general public$$fUnrestricted
000089679 5203_ $$aThe Tn antigen (GalNAc-a-1-O-Thr/Ser) is a well-known tumor-associated carbohydrate determinant. The use of glycopeptides that incorporate this structure has become a significant and promising niche of research owing to their potential use as anticancer vaccines. Herein, the conformational preferences of a glycopeptide with an unnatural Tn antigen, characterized by a threonine decorated with an sp2-iminosugar-type a-GalNAc mimic, have been studied both in solution, by combining NMR spectroscopy and molecular dynamics simulations, and in the solid state bound to an anti-mucin-1 (MUC1) antibody, by X-ray crystallography. The Tn surrogate can mimic the main conformer sampled by the natural antigen in solution and exhibits high affinity towards anti-MUC1 antibodies. Encouraged by these data, a cancer vaccine candidate based on this unnatural glycopeptide and conjugated to the carrier protein Keyhole Limpet Hemocyanin (KLH) has been prepared and tested in mice. Significantly, the experiments in vivo have proved that this vaccine elicits higher levels of specific anti-MUC1 IgG antibodies than the analog that bears the natural Tn antigen and that the elicited antibodies recognize human breast cancer cells with high selectivity. Altogether, we compile evidence to confirm that the presentation of the antigen, both in solution and in the bound state, plays a critical role in the efficacy of the designed cancer vaccines. Moreover, the outcomes derived from this vaccine prove that there is room for exploring further adjustments at the carbohydrate level that could contribute to designing more efficient cancer vaccines.
000089679 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/SAF2016-76083-R$$9info:eu-repo/grantAgreement/ES/MICINN/RTI2018-099592-B-C21$$9info:eu-repo/grantAgreement/ES/MICINN/RTI2018-097609-B-C21$$9info:eu-repo/grantAgreement/ES/MEC/CTQ2013-44367-C2-2-P$$9info:eu-repo/grantAgreement/ES/MEC/BFU2016-75633-P$$9info:eu-repo/grantAgreement/EC/FP7/283570/EU/Transnational access and enhancement of integrated Biological Structure determination at synchrotron X-ray radiation facilities/BIOSTRUCT-X$$9info:eu-repo/grantAgreement/ES/DGA/LMP58-18$$9info:eu-repo/grantAgreement/ES/DGA/E34-R17
000089679 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttp://creativecommons.org/licenses/by-nc/3.0/es/
000089679 590__ $$a9.825$$b2020
000089679 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b22 / 178 = 0.124$$c2020$$dQ1$$eT1
000089679 592__ $$a3.686$$b2020
000089679 593__ $$aChemistry (miscellaneous)$$c2020$$dQ1
000089679 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000089679 700__ $$aNavo, C.D.
000089679 700__ $$0(orcid)0000-0002-5736-5452$$aCastro-López, J.
000089679 700__ $$aGuerreiro, A.
000089679 700__ $$aJiménez-Moreno, E.
000089679 700__ $$aSánchez Fernández, E.M.
000089679 700__ $$aGarcía-Martín, F.
000089679 700__ $$aHinou, H.
000089679 700__ $$aNishimura, S.I.
000089679 700__ $$aGarcía Fernández, J.M.
000089679 700__ $$aMellet, C.O.
000089679 700__ $$aAvenoza, A.
000089679 700__ $$aBusto, J.H.
000089679 700__ $$aBernardes, G.J.L.
000089679 700__ $$0(orcid)0000-0002-3122-9401$$aHurtado-Guerrero, R.$$uUniversidad de Zaragoza
000089679 700__ $$aPeregrina, J.M.
000089679 700__ $$aCorzana, F.
000089679 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000089679 773__ $$g11, 15 (2020), 3996-4006$$pChem. sci.$$tChemical Science$$x2041-6520
000089679 8564_ $$s1172888$$uhttps://zaguan.unizar.es/record/89679/files/texto_completo.pdf$$yVersión publicada
000089679 8564_ $$s70457$$uhttps://zaguan.unizar.es/record/89679/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000089679 909CO $$ooai:zaguan.unizar.es:89679$$particulos$$pdriver
000089679 951__ $$a2021-09-02-09:22:31
000089679 980__ $$aARTICLE