title: Antisense inhibition of human telomerase by phosphorothioate oligonucleotide-peptide conjugates.
abstract: Oligonucleotides can be covalently linked to peptides composed of any sequence of amino acids by SPFC. The peptides incorporated into the conjugates include nuclear localizing signals (NLS), nuclear export signals (NES), membrane fusion domain of some viral proteins and some designed peptides with amphipathic character. Evaluation of biological properties of DNA-peptide conjugates indicated that (a) the conjugates could bind to target RNA and dsDNA with increased affinity, (b) the conjugates were more resistant to cellular nuclease degradation, (c) the conjugates-RNA hybrids could activate RNase H as effective as native oligonucleotides, (d) the conjugates with fusion peptides showed largely enhanced cellular uptake, (e) the conjugates with NLS could be predominantly delivered into cell nucleus, (f) the conjugates with NES could be localized in cytoplasm. As a result, antisense oligonucleotides conjugated with NLS could inhibit human telomerase in human leukemia cells much more strongly than phosphorothioate oligonucleotides.
authors.affiliation: Department of Biological and Environmental Chemistry, School of Humanity-Oriented Science and Engineering, Kinki University, Iizuka, Fukuoka 820-8555, Japan.
authors.forename: Irmina
authors.initials: I
authors.lastname: Diala
authors.forename: Satoshi
authors.initials: S
authors.lastname: Murao
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujii
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D054735:Phosphorothioate Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals; D016376:Oligonucleotides, Antisense; D010455:Peptides; D054735:Phosphorothioate Oligonucleotides; D019098:Telomerase