title: Promotion of double-duplex invasion of peptide nucleic acids through conjugation with nuclear localization signal peptide.
abstract: Pseudo-complementary peptide nucleic acid (pcPNA), as one of the most widely used synthetic DNA analogues, invades double-stranded DNA according to Watson-Crick rules to form invasion complexes. This unique mode of DNA recognition induces structural changes at the invasion site and can be used for a range of applications. In this paper, pcPNA is conjugated with a nuclear localization signal (NLS) peptide, and its invading activity is notably promoted both thermodynamically and kinetically. Thus, the double-duplex invasion complex is formed promptly at low pcPNA concentrations under high salt conditions, where the invasion otherwise never occurs. Furthermore, NLS-modified pcPNA is successfully employed for site-selective DNA scission, and the targeted DNA is selectively cleaved under conditions that are not conducive for DNA cutters using unmodified pcPNAs. This strategy of pcPNA modification is expected to be advantageous and promising for a range of in vitro and in vivo applications.
authors: Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8577 (Japan); Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904 (Japan); Present address: Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390-9041 (USA).
authors: Yuichiro
authors: Y
authors: Aiba
authors: Yuta
authors: Y
authors: Honda
authors: Makoto
authors: M
authors: Komiyama
mesh_terms: D020137:Base Pair Mismatch; D004247:DNA / Q000737:chemistry*; D053837:DNA Cleavage; D007700:Kinetics; D019913:Nuclear Localization Signals / Q000737:chemistry*; D020135:Peptide Nucleic Acids / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D019913:Nuclear Localization Signals; D020135:Peptide Nucleic Acids; D004247:DNA
keywords: DNA cleavage; DNA recognition; DNA structures; nucleic acids; peptides