Tanaka Kazuo, Tainaka Kazuki, Umemoto Tadashi, Nomura Akiko, Okamoto Akimitsu
Frontier Research System, RIKEN (The Institute of Physical and Chemical Research), Wako, Saitama 351-1098, Japan.
J Am Chem Soc. 2007 Nov 21;129(46):14511-7. doi: 10.1021/ja076140r. Epub 2007 Oct 27.
Nucleic acids often acquire new functions by forming a variety of complexes with metal ions. Osmium, in an oxidized state, also reacts with C5-methylated pyrimidines. However, control of the sequence specificity of osmium complexation with DNA is still immature, and the value of the resulting complexes is unknown. We have designed a bipyridine-attached adenine derivative for sequence-specific osmium complexation. Sequence-specific osmium complexation was achieved by hybridization of a short DNA molecule containing this functional nucleotide to a target DNA sequence and resulted in the formation of a cross-linked structure. The interstrand cross-link clearly distinguished methylated cytosines from unmethylated cytosines and was used to quantify the degree of methylation at a specific cytosine in the genome.
核酸常常通过与金属离子形成各种复合物来获得新功能。处于氧化态的锇也会与C5-甲基化嘧啶发生反应。然而，对锇与DNA络合的序列特异性的控制仍不成熟，所得复合物的价值也未知。我们设计了一种连接联吡啶的腺嘌呤衍生物用于序列特异性锇络合。通过将含有这种功能性核苷酸的短DNA分子与靶DNA序列杂交，实现了序列特异性锇络合，并导致形成交联结构。链间交联清楚地区分了甲基化胞嘧啶和未甲基化胞嘧啶，并用于量化基因组中特定胞嘧啶的甲基化程度。
