000095832 001__ 95832
000095832 005__ 20220322103047.0
000095832 0247_ $$2doi$$a10.1002/chem.202002067
000095832 0248_ $$2sideral$$a120400
000095832 037__ $$aART-2020-120400
000095832 041__ $$aeng
000095832 100__ $$aLuengo, A.
000095832 245__ $$aLuminescent Bimetallic IrIII /AuI Peptide Bioconjugates as Potential Theranostic Agents
000095832 260__ $$c2020
000095832 5060_ $$aAccess copy available to the general public$$fUnrestricted
000095832 5203_ $$aDiverse iridium peptide bioconjugates and the corresponding iridium/gold bimetallic complexes have been synthesized starting from a cyclometallated carboxylic acid substituted IrIII complex [Ir(ppy)2 (Phen-5-COO)] by solid phase peptide synthesis (SPPS). The selected peptide sequences were an enkephalin derivative Tyr-Gly-Gly-Phe-Leu together with the propargyl-substituted species Tyr-Gly-Pgl-Phe-Leu to allow gold coordination (Pgl: propyrgyl-glycine, HC=C-Gly), and a specific short peptide, Ala-Cys-Ala-Phen, containing a cysteine residue. Introduction of the gold center has been achieved via a click reaction with the alkynyl group leading to an organometallic Au-C(triazole) species, or by direct coordination to the sulfur atom of the cysteine. The photophysical properties of these species revealed predominantly an emission originating from the Ir complex, using mixed metal-to-ligand and ligand-to-ligand charge transfer excited states of triplet multiplicity. The formation of the peptide bioconjugates caused a systematic redshift of the emission profiles. Lysosomal accumulation was observed for all the complexes, in contrast to the expected mitochondrial accumulation triggered by the gold complexes. Only the cysteine-containing Ir/Au bioconjugate displayed cytotoxic activity. The absence of activity may be related to the lack of endosomal/lysosomal escape for the cationic peptide conjugates. Interestingly, the different coordination sphere of the gold atom may play a crucial role, as the Au-S(cysteine) bond may be more readily cleaved in a biological environment than the Au-C(triazole) bond, and thus the Au fragment could be released from or trapped in the lysosomes, respectively. This work represents a starting point in the development of bimetallic peptide bioconjugates as theranostics and in the knowledge of factors that contribute to anti-proliferative activity.
000095832 536__ $$9info:eu-repo/grantAgreement/ES/MICINN/RYC-2018-025872-I$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-104379RB-C21$$9info:eu-repo/grantAgreement/ES/MCIU/RTI2018-097836-J-I00$$9info:eu-repo/grantAgreement/ES/MCIU/RED2018-102471-T$$9info:eu-repo/grantAgreement/ES/MCIU/CTQ2016-75816-C2-1-P$$9info:eu-repo/grantAgreement/ES/DGA-FSE/E07-20R$$9info:eu-repo/grantAgreement/ES/MINECO/PID2019-104379RB-C21
000095832 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000095832 590__ $$a5.236$$b2020
000095832 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b52 / 178 = 0.292$$c2020$$dQ2$$eT1
000095832 592__ $$a1.687$$b2020
000095832 593__ $$aCatalysis$$c2020$$dQ1
000095832 593__ $$aOrganic Chemistry$$c2020$$dQ1
000095832 593__ $$aChemistry (miscellaneous)$$c2020$$dQ1
000095832 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000095832 700__ $$0(orcid)0000-0002-2315-9079$$aMarzo, I.$$uUniversidad de Zaragoza
000095832 700__ $$aReback, M.
000095832 700__ $$aDaubit, I.M.
000095832 700__ $$0(orcid)0000-0002-1218-7218$$aFernández-Moreira, V.$$uUniversidad de Zaragoza
000095832 700__ $$aMetzler-Nolte, N.
000095832 700__ $$0(orcid)0000-0003-0553-0695$$aGimeno, M.C.$$uUniversidad de Zaragoza
000095832 7102_ $$12010$$2760$$aUniversidad de Zaragoza$$bDpto. Química Inorgánica$$cÁrea Química Inorgánica
000095832 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000095832 773__ $$g26, 53 (2020), 12158-12167$$pChemistry (Weinh.)$$tChemistry - A European Journal$$x0947-6539
000095832 8564_ $$s772602$$uhttps://zaguan.unizar.es/record/95832/files/texto_completo.pdf$$yVersión publicada
000095832 8564_ $$s558566$$uhttps://zaguan.unizar.es/record/95832/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000095832 909CO $$ooai:zaguan.unizar.es:95832$$particulos$$pdriver
000095832 951__ $$a2022-03-22-10:16:28
000095832 980__ $$aARTICLE