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 polydiamidopropanoate (PDAP) dendrimers with different numbers of diaminopropanoate 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 by RP-HPLC, and characterized by MALDI-TOF mass spectroscopy.
Amirkhanov
N V
NV
Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Wickstrom
Eric
E
D001483:Base Sequence; D002614:Chelating Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D011905:Genes, ras / Q000235:genetics; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation* / Q000379:methods; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors
D002614:Chelating Agents; D006573:Heterocyclic Compounds, 1-Ring; D020135:Peptide Nucleic Acids; D010455:Peptides; D011108:Polymers; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid