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Facile protein conjugation of platinum for light-activated cytotoxic payload release
Cinzia Imberti1, Frederik Lermyte2, Emily P Friar1
1Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK. cinzia.imberti@warwick.ac.uk P.J.Sadler@warwick.ac.uk.
Abstract:
The novel Pt(iv) complex trans,trans-[Pt(N3)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.
