Luminescent Bimetallic IrIII /AuI Peptide Bioconjugates as Potential Theranostic Agents
Resumen: 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.
Idioma: Inglés
DOI: 10.1002/chem.202002067
Año: 2020
Publicado en: Chemistry - A European Journal 26, 53 (2020), 12158-12167
ISSN: 0947-6539

Factor impacto JCR: 5.236 (2020)
Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 52 / 178 = 0.292 (2020) - Q2 - T1
Factor impacto SCIMAGO: 1.687 - Catalysis (Q1) - Organic Chemistry (Q1) - Chemistry (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA-FSE/E07-20R
Financiación: info:eu-repo/grantAgreement/ES/MCIU/CTQ2016-75816-C2-1-P
Financiación: info:eu-repo/grantAgreement/ES/MCIU/RED2018-102471-T
Financiación: info:eu-repo/grantAgreement/ES/MCIU/RTI2018-097836-J-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2019-104379RB-C21
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RYC-2018-025872-I
Financiación: info:eu-repo/grantAgreement/ES/MINECO/PID2019-104379RB-C21
Tipo y forma: Article (Published version)
Área (Departamento): Área Química Inorgánica (Dpto. Química Inorgánica)
Área (Departamento): Área Biología Celular (Dpto. Bioq.Biolog.Mol. Celular)


Creative Commons You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. If you remix, transform, or build upon the material, you may not distribute the modified material.


Exportado de SIDERAL (2022-03-22-10:16:28)


Visitas y descargas

Este artículo se encuentra en las siguientes colecciones:
Articles



 Record created 2020-10-20, last modified 2022-03-22


Versión publicada:
 PDF
Rate this document:

Rate this document:
1
2
3
 
(Not yet reviewed)