Synthesis of PtIV-Biomolecule Conjugates through Click Chemistry

The azide-functionalized Pt-IV complex {(OC-6-34)-chlorido-(cyclobutane-1,1'-dicarboxylato)(cyclohexane-1R, 2R-diamine)[2-hydroxyethyl(2-{2-[2-(2-azidoethoxy) ethoxy]-ethoxy}ethyl)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 (Cu-I-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 17 alpha-ethynylestradiol. The title complex demonstrated very good compatibility with both CuAAC reaction and solidphase peptide synthesis conditions, making it a suitable anti-proliferative fragment for the design of nanovectors.