Guo Chuanxin, Kawamoto Yusuke, Asamitsu Sefan, Sawatani Yoshito, Hashiya Kaori, Bando Toshikazu, Sugiyama Hiroshi
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan.
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan.
Bioorg Med Chem. 2015 Feb 15;23(4):855-60. doi: 10.1016/j.bmc.2014.12.025. Epub 2014 Dec 30.
N-Methylpyrrole (Py)-N-methylimidazole (Im) polyamides are organic molecules that can recognize predetermined DNA sequences in a sequence-specific manner. Human telomeres contain regions of (TTAGGG)n repetitive nucleotide sequences at each end of chromosomes, and these regions protect the chromosome from deterioration or from fusion with neighboring chromosomes. The telomeres are disposable 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 in 2001. Here, we synthesized three types of Py-Im polyamides 1-3 based on TH59 for specific recognition of human telomere repeat sequences. Thermal melting temperature (Tm) measurements and surface plasmon resonance analysis were used to evaluate the abilities of the three types of Py-Im polyamides to discriminate between three kinds of DNA sequences. Significantly, the results showed that polyamides 1 and 2 have better affinities to TTAAGG than to TTAGGG. In contrast, polyamide 3 displayed good specificity to human telomere sequence, TTAGGG, as expected on the basis of Py-Im binding rules.
N-甲基吡咯（Py）-N-甲基咪唑（Im）聚酰胺是一类能够以序列特异性方式识别特定DNA序列的有机分子。人类端粒在染色体的两端包含（TTAGGG）n重复核苷酸序列区域，这些区域可保护染色体免于退化或与相邻染色体融合。端粒是染色体末端的一次性缓冲区域，在细胞分裂过程中会被截短。Laemmli小组在2001年报道了能够识别人类端粒序列的串联发夹状Py-Im聚酰胺TH59。在此，我们基于TH59合成了三种类型的Py-Im聚酰胺1-3，用于特异性识别人类端粒重复序列。通过热熔解温度（Tm）测量和表面等离子体共振分析来评估这三种类型的Py-Im聚酰胺区分三种DNA序列的能力。值得注意的是，结果表明聚酰胺1和2对TTAAGG的亲和力比对TTAGGG的亲和力更好。相比之下，根据Py-Im结合规则，聚酰胺3对人类端粒序列TTAGGG表现出良好的特异性。
