title: Specific alkylation of human telomere repeats by hairpin pyrrole-imidazole polyamide.
abstract: A novel hairpin polyamide-cyclopropapyrroloindole (CPI) conjugate PyImImIm-gamma-PyPyPyLDu86 (conjugate 11), which targets human telomere repeats d(TTAGGG)(n)/d(CCCTAA)(n), was synthesized. High resolution denaturing polyacrylamide gel electrophoresis using 44 bp DNA fragments and HPLC product analysis of a synthetic nonanucleotide demonstrated that conjugate 11 alkylates the target adenine in the telomere repeats, 5'-CCCTAA-3'. Examination of the antitumor activity of conjugate 11 using a panel of 39 cancer cell lines demonstrated that the average concentration of conjugate 11 required for 50% growth inhibition was 5.75 microM, which is superior to pepleomycin and bleomycin and comparable to cisplatin.
authors.affiliation: Division of Biofunctional Molecules, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Surugadai, Kanda, Chiyoda, Tokyo 101-0062, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Takahashi
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Bando
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000225:Adenine / Q000737:chemistry; D000478:Alkylation; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D009690:Nucleic Acid Conformation; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009841:Oligonucleotides / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry*; D012091:Repetitive Sequences, Nucleic Acid; D016615:Telomere / Q000737:chemistry* / Q000235:genetics
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007093:Imidazoles; D009757:Nylons; D009841:Oligonucleotides; D011758:Pyrroles; C029899:imidazole; D004247:DNA; D000225:Adenine