1995年8月
SEQUENCE PREFERENCE FOR STRAND CLEAVAGE OF GAPPED DUPLEXES BY DYNEMICIN-A - POSSIBLE MECHANISM OF SEQUENCE-DEPENDENT DOUBLE-STRANDED BREAKS
BIOCHEMISTRY
- ,
- ,
- 巻
- 34
- 号
- 31
- 開始ページ
- 9944
- 終了ページ
- 9950
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1021/bi00031a017
- 出版者・発行元
- AMER CHEMICAL SOC
A double-stranded DNA cleavage mechanism by a novel enediyne type antitumor antibiotic, dynemicin A, has been investigated through sequence-dependent strand breakage of a series of duplexes containing a single nucleotide gap. We found that (1) dynemicin A breaks specifically at the S'-shifted position by one base opposite the gap, (2) the strong cleavage is detected at 5'-Pu Pu/3'-PyPuPy sequences, and (3) dynemicin H (aromatized form of dynemicin A) gives only a small inhibition effect (20%) on the cleavage of gapped duplex by dynemicin A. The long half-life of aromatization of dynemicin A (118 min, in the presence of DNA) obtained from HPLC analysis provides enough time for the second cleavage. The present results strongly indicate a two-step mechanism for the double-stranded DNA scission of dynemicin A. Namely, this double-stranded break is caused by two drug molecules, each of which cuts one DNA strand.
- リンク情報
-
- DOI
- https://doi.org/10.1021/bi00031a017
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200902100468189964
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/7632693
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:A1995RN73200017&DestApp=WOS_CPL
- ID情報
-
- DOI : 10.1021/bi00031a017
- ISSN : 0006-2960
- J-Global ID : 200902100468189964
- PubMed ID : 7632693
- Web of Science ID : WOS:A1995RN73200017