2000年7月26日
Structural basis for reaction mechanism and drug delivery system of chromoprotein antitumor antibiotic C-1027
Journal of the American Chemical Society
- ,
- ,
- 巻
- 122
- 号
- 29
- 開始ページ
- 6848
- 終了ページ
- 6854
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1021/ja994323a
- 出版者・発行元
- AMER CHEMICAL SOC
Antitumor antibiotic C-1027, which is regarded as a natural model of a drug delivery system, consists of a carrier apoprotein (Apo) and an enediyne chromophore (Chr). We have compared three solution structures of the DNA - Chr complex, Apo - Chr complex, and free Chr determined by high-resolution NMR experiments. The guest molecule, C-1027 chromophore, showed two distinct binding modes fitted to binding sites of the hosts (target DNA and carrier Apo). The novel Chr interacts with DNA through its benzoxazolinate and aminosugar moieties, and also with Apo through the benzoxazolinate and macrocyclic moieties. The superposition of Chrs in these three states clearly revealed conformational deviation of the 16-membered macrocyclic moiety containing an intra-chlorophenol ring. Ab initio calculations supported good correlation between the reactivity and the conformational alteration of Chr induced in the hosts. The present results provide a molecular basis and implication for the host-recognition mode, the reaction mechanism, and the drug delivery system of chromoprotein C-1027.
- リンク情報
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- DOI
- https://doi.org/10.1021/ja994323a
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200902127551438564
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000088522700006&DestApp=WOS_CPL
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=0034718061&origin=inward
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=0034718061&origin=inward
- ID情報
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- DOI : 10.1021/ja994323a
- ISSN : 0002-7863
- J-Global ID : 200902127551438564
- SCOPUS ID : 0034718061
- Web of Science ID : WOS:000088522700006