Luminescent Bimetallic IrIII/AuI Peptide Bioconjugates as Potential Theranostic Agents |
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Authors: | Dr. Andrés Luengo Dr. Isabel Marzo Dr. Matthew Reback Isabelle M. Daubit Dr. Vanesa Fernández-Moreira Prof. Dr. Nils Metzler-Nolte Prof. Dr. M. Concepción Gimeno |
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Affiliation: | 1. Departamento de Química Inorgánica, Instituto de Síntesis QuímicayCatálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, 50009 Zaragoza, Spain;2. Departamento de Bioquímica y Biología Celular, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain;3. Inorganic Chemistry I—Bioinorganic Chemistry, Faculty of Chemistry and Biochemistry, Ruhr-Universität Bochum, Universitätsstrasse 150, 44801 Bochum, Germany |
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Abstract: | Diverse 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. |
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Keywords: | bimetallic compounds cell imaging gold iridium peptide bioconjugates theranostic agents |
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