Luminescent bimetallic Ir\(^{III}\)/Au\(^{I}\) peptide bioconjugates as potential theranostic agents
- Diverse iridium peptide bioconjugates and the corresponding iridium/gold bimetallic complexes have been synthesized starting from a cyclometallated carboxylic acid substituted IrIr\(^{III}\) 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.
Author: | Andrés LuengoGND, Isabel MarzoORCiDGND, Matthew RebackGND, Isabelle DaubitGND, Vanesa Fernández-MoreiraORCiDGND, Nils Metzler-NolteORCiDGND, M. Concepción GimenoORCiDGND |
---|---|
URN: | urn:nbn:de:hbz:294-99045 |
DOI: | https://doi.org/10.1002/chem.202002067 |
Parent Title (English): | Chemistry - A European journal |
Publisher: | Wiley-VCH |
Place of publication: | Hoboken, New Jersey |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2023/05/23 |
Date of first Publication: | 2020/06/16 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | bimetallic compounds; cell imaging; gold; iridium; peptide bioconjugates; theranostic agents |
Volume: | 26 |
Issue: | 53 |
First Page: | 12158 |
Last Page: | 12167 |
Note: | Dieser Beitrag ist auf Grund des DEAL-Wiley-Vertrages frei zugänglich. |
Institutes/Facilities: | Lehrstuhl für Anorganische Chemie I, Bioanorganische Chemie |
Dewey Decimal Classification: | Naturwissenschaften und Mathematik / Chemie, Kristallographie, Mineralogie |
open_access (DINI-Set): | open_access |
faculties: | Fakultät für Chemie und Biochemie |
Licence (English): | Creative Commons - CC BY-NC-ND 4.0 - Attribution-NonCommercial-NoDerivatives 4.0 International |