1. NMR Studies on Antitumor Drug Candidates, Berberine and Berberrubine
- Author
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In Kwon Chung, Miran Kang, Jinwon Jung, Young Wook Jeon, and Weontae Lee
- Subjects
Drug ,biology ,Stereochemistry ,Chemistry ,media_common.quotation_subject ,Topoisomerase ,Chemical structure ,General Chemistry ,chemistry.chemical_compound ,Berberine ,Biochemistry ,Dna cleavage ,Helix ,biology.protein ,Protein network ,DNA ,media_common - Abstract
Protein Network Research Center, Yonsei University, Seoul 120-749, KoreaReceived August 16, 2001Berberine and berberrubine, which display antitumor activity, have also demonstrated distinct enzyme-poisoning activities by stabilizing topoisomerase II-DNA cleavable complexes. The protoberberineberberrubine differs in chemical structure with berberine at only one position, however, it shows a prominentactivity difference from berberine. Solution structures of berberine and berberrubine determined by NMRspectroscopy are similar, however, the minor structural rearrangement has been observed near 19 methoxy orhydroxyl group. We suggest that the DNA cleavage activities of topoisomerase II poisons could be correlatedwith both chemical environments and minor structural change together with hydrophobicity of interacting sidechains of drugs with DNA molecule.Keywords : Berberine, Berberrubine, Anti-tumor drug, ROESY, NMR.IntroductionOne of the most important molecular targets for anti-tumor drugs is DNA topoisomerase II, which forms acovalent linkage to both strands of the DNA helix bybreaking and resealing the sugar-phosphate backbone bondsof DNA.
- Published
- 2002
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