Rational design of specific binding hairpin Py–Im polyamides targeting human telomere sequences》.pdf

Bioorganic Medicinal Chemistry 23 (2015) 855–860 Contents lists available at ScienceDirect Bioorganic Medicinal Chemistry journal homepage: www.else /locate/bmc Rational design of specific binding hairpin Py–Im polyamides targeting human telomere sequences Chuanxin Guo a, Yusuke Kawamoto a, Sefan Asamitsu a, Yoshito Sawatani a, Kaori Hashiya a, Toshikazu Bando a,⇑, Hiroshi Sugiyama a,b,⇑ a Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan b Institute for Integrated Cell-Materials Science (iCeMS), Kyoto University, Sakyo, Kyoto 606-8501, Japan a r t i c l e i n f o a b s t r a c t Article history: N-Methylpyrrole (Py)–N-methylimidazole (Im) polyamides are organic molecules that can recognize pre- Received 27 October 2014 determined DNA sequences in a sequence-specific manner. Human telomeres contain regions of Revised 12 December 2014 (TTAGGG)n repetitive nucleotide sequences at each end of chromosomes, and these regions protect the Accepted 13 December 2014 chromosome from deterioration or from fusion with neighboring chromosomes. The telomeres are dis- Available online 30 December 2014 posable buffers at the ends of chromosomes that are truncated during cell division. Tandem hairpin Py–Im polyamide TH59, which recognizes human telomere sequences, was reported by Laemmli’s group Keywords: in 2001. Here, we synthesi