著者

橋本 祐一 首藤 紘一

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.43, no.10, pp.908-920, 1985 (Released:2009-11-13)

参考文献数

49

被引用文献数

2

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Bis-intercalators and hemin-intercalators (Hemin-Glu-P-1's) which recognize and/or cleave DNA were designed and synthesized. 2-Aminodipyrido [1, 2-a : 3', 2' -d] imidazoles (Glu-P's) which are potent muta-carcinogens isolated from a pyrolysate of L-glutamic acid were used as intercalator moieties. Bis-intercalators possess extremely high affinity toward double stranded DNA and stabilize the double helix structure of DNA from heat denaturation effectively. Hemin-Glu-P-1's cleaved DNA at G-C and G-T sequences preferentially. Glu-P-1 moiety which recognizes DNA by intercalation and a functional group which can be an intramolecular fifth ligand of the ferrous ion in the hemin moiety are required for strong DNA-cleaving ability. The mode of DNA-cleaving reaction of Hemin-Glu-P-1's is quite similar to that of bleomycin (BLM). In other words, Hemin-Glu-P-1's are functional analogs of BLM. The mechanism of DNA cleavage by Hemin-Glu-P-1's and by BLM is not single. One of the mechanisms involves two bases elimination from the DNA.