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Facile protein conjugation of platinum for light-activated cytotoxic payload release

The novel Pt(iv) complex trans,trans-[Pt(N(3))(2)(Py)(2)(OH)(OCO-(PEG)(2)-NHCSNH-Ph-NCS)] (Pt4) conjugates to the side chain of lysine amino acids in proteins under mild conditions. Reaction with myoglobin generated a bioconjugate that was stable in the dark, but released a Pt(iv) prodrug upon visib...

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Detalles Bibliográficos
Autores principales: Imberti, Cinzia, Lermyte, Frederik, Friar, Emily P., O'Connor, Peter B., Sadler, Peter J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330822/
https://www.ncbi.nlm.nih.gov/pubmed/34250984
http://dx.doi.org/10.1039/d1cc02722k
Descripción
Sumario:The novel Pt(iv) complex trans,trans-[Pt(N(3))(2)(Py)(2)(OH)(OCO-(PEG)(2)-NHCSNH-Ph-NCS)] (Pt4) conjugates to the side chain of lysine amino acids in proteins under mild conditions. Reaction with myoglobin generated a bioconjugate that was stable in the dark, but released a Pt(iv) prodrug upon visible light irradiation. A similar procedure was used to conjugate Pt4 to the antibody trastuzumab, resulting in the first photoactivatable Pt(iv)-antibody conjugate, demonstrating potential for highly selective cancer phototherapy.