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.
Highlights
The novel Pt(IV) complex trans,trans-[Pt(N3)2(Py)2(OH)(OCO-(PEG)2NHCSNH-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
Pt4 was synthesised in 3 steps from the prototype complex Pt1
Summary
The novel Pt(IV) complex trans,trans-[Pt(N3)2(Py)2(OH)(OCO-(PEG)2NHCSNH-Ph-NCS)] (Pt4) conjugates to the side chain of lysine amino acids in proteins under mild conditions. Unlike traditional Pt(IV) prodrugs, photoactivatable Pt(IV) azido complexes are inert and non-toxic in the presence of bio-reductants, but release cytotoxic Pt(II) species upon irradiation with visible light, providing spatial and temporal control of their chemotherapeutic activity.[9] Derivatisation of these complexes can provide, for example, cancer-targeting peptide conjugates.[10,11] A protein adduct has been synthesised, which exploits a pendant biotin moiety to attach the Pt(IV) agent to avidin, utilising the high biotin–avidin affinity.[12]
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