Dual-Bioorthogonal Catalysis by a Palladium Peptide Complex.
J Med Chem
; 66(5): 3301-3311, 2023 03 09.
Article
em En
| MEDLINE
| ID: mdl-36820649
ABSTRACT
Artificial metalloenzymes (ArMs) enrich bioorthogonal chemistry with new-to-nature reactions while limiting metal deactivation and toxicity. This enables biomedical applications such as activating therapeutics in situ. However, while combination therapies are becoming widespread anticancer treatments, dual catalysis by ArMs has not yet been shown. We present a heptapeptidic ArM with a novel peptide ligand carrying a methyl salicylate palladium complex. We observed that the peptide scaffold reduces metal toxicity while protecting the metal from deactivation by cellular components. Importantly, the peptide also improves catalysis, suggesting involvement in the catalytic reaction mechanism. Our work shows how a palladium-peptide homogeneous catalyst can simultaneously mediate two types of chemistry to synthesize anticancer drugs in human cells. Methyl salicylate palladium LLEYLKR peptide (2-Pd) succeeded to simultaneously produce paclitaxel by depropargylation, and linifanib by Suzuki-Miyaura cross-coupling in cell culture, thereby achieving combination therapy on non-small-cell lung cancer (NSCLC) A549 cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
/
Neoplasias Pulmonares
/
Metaloproteínas
Limite:
Humans
Idioma:
En
Revista:
J Med Chem
Ano de publicação:
2023
Tipo de documento:
Article