Synthesis and characterisation of a novel mono functionalisable Pt(IV) oxaliplatin-type complex and its peptide conjugate

The synthesis and characterisation of a novel Pt(IV) monocarboxy precursor complex c,c,t-[Pt(DACH)(Ox)(OEt)(Suc)], which can be employed to synthesise mono functionalised Pt(IV) oxaliplatin-based complexes is reported. Reaction of c,c,t-[Pt(DACH)(Ox)(OEt)(Suc)] with a tumour penetrating peptide, TPP, afforded the corresponding novel monofunctionalised Pt(IV) peptide conjugate c,c,t-[Pt(DACH)(Ox)(OEt)(SucTPP)] in high purity. Conjugation of TPP to c,c,t-[Pt(DACH)(Ox)(OEt)(Suc)] was demonstrated to ameliorate its inherent cytotoxicity fifteen fold in the Pt sensitive HCT116 colorectal cancer cell line and two fold in the relatively resistant HT29 colorectal cancer cell line.