Synthesis of novel polydiamidopropanoate dendrimer PNA-peptide chimeras for non-invasive magnetic resonance imaging of cancer

A variety of dendrimers can be conjugated to oligonucleotides to increase the number of contrast paramagnetic atoms (e.g., gadolinium or dysprosium) per probe. Thus, it was of interest to test a route for assembly of chelating dendrimer branches directly on the N-termini of peptide nucleic acid (PNA)peptide chimeras by continuous solid-phase coupling on polymer supports. Dendrimer-PNA-peptides complementary to 12 nt Of mutant KRAS mRNA have been prepared with a C-terminal insulin-like growth factor 1 (IGF1) analog d(Cys-Ser-Lys- Cys) and N-terminal polydiamidapropanoate (PDAP) dendrimers with different numbers of diaminapropanoate residues. 1, 4, 7, 10-Tetraazacyclododecane-1,4,7, 10-tetraacetic acid (DOTA) chelating moieties were then coupled to PDAP dendrimer-PNA-peptide chimeras before cleavage from the polymer supports. The DOTA -PDAP-PNA -peptide probes with 1, 2 4, 8, or 16 amino (or DOTA) moieties were cleaved, purified 4 RP-HPLC, and characterized MALD1-TOF mass spectroscopy.