Synthesis of PtIV-Biomolecule Conjugates through Click Chemistry

The azide-functionalized PtIV complex (OC-6–34)-chlorido(cyclobutane-1,1′-dicarboxylato)(cyclohexane-1R,2R-diamine)[2-hydroxyethyl(2-2-[2-(2-azidoethoxy)ethoxy]ethoxyethyl)carbamate]platinum(IV) was synthesized and characterized to obtain a starting complex that was suitable for coupling with appropriate biological carriers in a drug targeting and delivery strategy. The following click reaction (CuI-catalyzed Huisgen cycloaddition, CuAAC) was successfully applied for coupling with three different model biomolecules that can be exploited for selective targeting of the platinum conjugate toward tumor cells; i.e., the amino acid alanine and the dipeptide lysine-alanine, both previously alkyne-functionalized with pent-4-ynoic acid, and the hormone 17α-ethynylestradiol. The title complex demonstrated very good compatibility with both CuAAC reaction and solid-phase peptide synthesis conditions, making it a suitable antiproliferative fragment for the design of nanovectors.