Synthesis and cytotoxicity of a bimetallic ruthenocene dicobalt-hexacarbonyl alkyne peptide bioconjugate

Abstract

Organometallic conjugates of receptor-targeting peptides are proposed as interesting candidates for novel cancer therapies since they are capable of targeting a specific kind of cell. Here, we have synthesised a dicobalt hexacarbonyl alkyne compound linked to the neurotensin peptide hormone. In order to circumvent synthetic difficulties encountered when adding a cobalt carbonyl moiety onto the hydrophilic alkyne peptide, and to enhance the cellular uptake we functionalised the alkyne neurotensin(8-13) fragment (NT) first N-terminally by ruthenocene carboxylic acid to form the metallocene-alkyne-NT conjugate 3, before adding Co₂(CO)₈ to a propargyl glycine residue to form the Co-alkyne derivative 4. Compound 4 represents the first heterobimetallic organometallic peptide conjugate reported to date. It shows moderate cytotoxicity against HeLa, PT45 and HepG2 cell lines.