Conjugated Platinum(II)-Peptide Complexes for Targeting Integrin Receptors

Targeted drug delivery is currently an active area of research in cancer therapy. It offers two major advantages over traditional chemotherapy: (1) it reduces the severe side effects avoiding damage to the normal tissue, and (2) it can prevent drug resistance which is a real limit for cytoxic platinum complexes applications [1]. The selective delivery could be reach driving the drugs through a bioactive or macromolecular vector. Peptides able to recognize receptors are a very amazing tools to perform this task. They must contain a coordinating arm capable of binding the cytotoxic Pt-moiety without losing the capability to bind receptors. The integrins αvβ3 and αvβ5 are highly expressed in tumor-induced angiogenesis [2], making them attractive targets for therapeutic intervention. We have designed, synthesized and tested a new platinum conjugate RGD cyclic sequence c(RGDfK). The platinum was anchored to the peptide moiety through a bidentate chelating agents linked to a hydrophilic ethoxylic linker. Both the synthesis of the peptide moiety and the platinum coordination were carried out on solid phase adapting the Fmoc strategy. The conjugate was purified by recrystallization and characterized by LC and ESI mass spectrometry. Biological assays on different human melanoma line cells overexpressing integrin receptors will be carried out in order to demonstrate the increase of the efficacy of the platinum tethered complex versus the free complex