Synthesis of Dithio-Diphosphine (P₂S₂COOH)-Based Bifunctional Chelating Agent. Its Coupling Reactions with Peptide Analogs and Steroids

Abstract

Bifunctional chelating agents are important in the development of site-specific radiopharmaceuticals for diagnosis and therapy of cancer. Recently. our Laboratory has developed a new dithio-diphosphine (P₂S₂COOH)-based bifunctional chelating agent [1]. Its coupling to biologically important molecules such as peptide analogs and steroids have been investigated in detail (Scheme I). The intermediate compound P₂S₂ phosphine hydride 3 was synthesized as described in scheme 1 [1]. The coupling of 3 with steroids such as 2/4 amino estrone/estrodiol and the peptide analog GlyGlyOEt was undertaken using peptide the coupling reagent HBTU in the presence of triethylamine. Furthermore. the P₂S₂GlyGlyOEt phosphine hydride was formylated using formaldehyde in ethanol and then complexed with a Re(V) precursor to yield the new Re(V) bioconjugate 5. This offers a potential mute to label biologically active peptides with radionuclides such as Tc-99m and Re-186/188 for use in cancm diagnosis and/or therapy.