Bioorganometallic platinum(II)-peptide nucleic acid conjugates

Peptide nucleic acids (PNAs) are mimics of natural nucleic acids able to target complementary DNA or RNA strands with high sequence specificity and affinity, and are therefore potential excellent candidates in diagnostics, antisense and antigene therapy.1 In place of the ribose phosphodiester backbone of DNA and RNA, PNAs contain a pseudopeptide backbone, composed of N-(2-aminoethyl)glycine units, on which the four nucleobases are inserted. PNAs display high chemical and enzymatic stability towards nucleases, but unmodified PNAs often exhibit low cellular uptake and this feature constitutes a drawback towards its effective use in therapy. One of the strategies to overcome this problem is the conjugation of PNA to metal complexes that can modify their intrinsic physico-chemical and spectroscopic properties.2 In our ongoing studies on PNAs, we have focused our attention on the development of novel bioorganometallic metal-PNA conjugates that can be employed as dual activity agents for the synergic treatment of cancer or bacterial infections, combining antisense therapy based on PNAs and photodynamic therapy (PDT) related to the use of the metal complex as the photosensitizer able to generate cytotoxic singlet oxygen (1O2) under appropriate excitation light.3 Among others, Pt(II)complexes with a cyclometallated terdentate ligand of the NCN type which affords the platinum center a rigid coordination environment represent promising photosensitizers, being the most luminescent Pt emitters in solution at room temperature. In this communication we will report our first studies on the innovative bioorganometallic metal-PNA conjugates formed by model PNA sequences covalently linked to Pt(II)- chloride complexes with a 1,3-di(2-pyridyl)benzene ligand, (Figure 1). The synthetic strategies to prepare these innovative PNA-conjugates will be described along with their photophysical characterization including absorption and emission studies.