Synthesis and characterisation of a ruthenocenoyl bioconjugate with the cyclic octapeptide octreotate

The reaction of activated ruthenocene carboxylic acid with the resin-bound peptide octreotate yields, after cleavage and purification by preparative HPLC, the first ruthenocenoyl peptide bioconjugate 1. Octreotate is a chemically stabilized analogue of somatostatine. It is a cyclic octapeptide with a disulfide bond and has been previously used for molecular diagnostics due to the fact that somatostatine receptors are over-expressed by a variety of cancer cells. Conjugate 1 was obtained in good yield and purified by preparative HPLC to >95% purity as judged by analytical HPLC. It has been identified by HPLC, IR and mass spectrometry (ESI and MALDI-TOF). The peptide’s NMR signals are assigned by standard 2D methods. In addition, the 1H NMR spectrum of 1 shows characteristic signals for the metallocene between 5.1 and 4.3 ppm. Compound 1 thus is a new example of tumor-targeted organometallic ruthenium bioconjugates.

Graphical abstractThe solid phase synthesis of the cyclic octapeptide octreotate with covalently attached ruthenocene is described. Conjugates of this kind have potential as targeted metal-based drugs.Figure optionsDownload full-size imageDownload as PowerPoint slide