Synthesis and Structure-Activity Relationship Study of Organometallic Bioconjugates of the Cyclic Octapeptide Octreotate

The chemically stabilized somatostatin-derived cyclic octapeptide octreotate has a number of interesting applications in medicinal chemistry. Here, a number of different organometallic derivatives of octreotate were prepared, and their properties were investigated. Specifically, we report the synthesis and characterization of ruthenocene, ferrocene, and cobaltocenium octreotate derivatives and their fluorophore-labeled conjugates as well as a dicobalt hexacarbonyl alkyne functionalized octreotate. To provide further insights into their characteristics, the logP values and electrochemical properties of the novel metal conjugates were compared. For biological activity, we determined their toxicity in three different cell lines. Cellular uptake and colocalization of selected compounds were studied by fluorescence microscopy with particular focus on efficiency and specificity of their uptake through the somatostatin receptor SSTR to elucidate the value of the metallocene head group for its potential use as a nontoxic and universal peptide label.