DNA binding mode of the isoquinoline alkaloid berberine with the deoxyoligonucleotide d(GCCGTCGTTTTACA)2

Hye Seo Park, Eun Hee Kim, Yoon Hui Sung, Mi Ran Kang, In Kwon Chung, Chaejoon Cheong, Weon Tae Lee

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The ability of protoberberine alkaloids, berberine and berberrubine, to act as topoisomerase II poisons is linked to the anti-cancer activity. Minor alterations in structure have a significant effect on their relative activity. Berberine, which has methoxy group at the 19-position, is significantly less potent than berberrubine. Several observations support non-specific binding to HP14 by the berberine: (i) nonspecific upfield changes in 1H chemical shift for protons of the berberine; (ii) the broadening of imino protons of HP14 upon binding of the berberine; (iii) very small increases in duplex melting temperature in the presence of the berberine. Our results reveal that substitution of a hydroxyl group to a methoxy group on the 19-position, thereby converting the berberrubine to the berberine is associated with a non-specific DNA binding affinity and a reduced topoisomerase II poisoning. The presence of a bulky 19-methoxy substituent decreases intercalating properties of berberine and makes it inactive as topoisomerase II poison.

Original languageEnglish
Pages (from-to)539-544
Number of pages6
JournalBulletin of the Korean Chemical Society
Volume25
Issue number4
DOIs
Publication statusPublished - 2004 Apr 20

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Berberine Alkaloids
Berberine
DNA
Type II DNA Topoisomerase
Poisons
Protons
Chemical shift
isoquinoline
Hydroxyl Radical
Melting point
Substitution reactions

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

Cite this

Park, Hye Seo ; Kim, Eun Hee ; Sung, Yoon Hui ; Kang, Mi Ran ; Chung, In Kwon ; Cheong, Chaejoon ; Lee, Weon Tae. / DNA binding mode of the isoquinoline alkaloid berberine with the deoxyoligonucleotide d(GCCGTCGTTTTACA)2. In: Bulletin of the Korean Chemical Society. 2004 ; Vol. 25, No. 4. pp. 539-544.
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DNA binding mode of the isoquinoline alkaloid berberine with the deoxyoligonucleotide d(GCCGTCGTTTTACA)2. / Park, Hye Seo; Kim, Eun Hee; Sung, Yoon Hui; Kang, Mi Ran; Chung, In Kwon; Cheong, Chaejoon; Lee, Weon Tae.

In: Bulletin of the Korean Chemical Society, Vol. 25, No. 4, 20.04.2004, p. 539-544.

Research output: Contribution to journalArticle

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AU - Park, Hye Seo

AU - Kim, Eun Hee

AU - Sung, Yoon Hui

AU - Kang, Mi Ran

AU - Chung, In Kwon

AU - Cheong, Chaejoon

AU - Lee, Weon Tae

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N2 - The ability of protoberberine alkaloids, berberine and berberrubine, to act as topoisomerase II poisons is linked to the anti-cancer activity. Minor alterations in structure have a significant effect on their relative activity. Berberine, which has methoxy group at the 19-position, is significantly less potent than berberrubine. Several observations support non-specific binding to HP14 by the berberine: (i) nonspecific upfield changes in 1H chemical shift for protons of the berberine; (ii) the broadening of imino protons of HP14 upon binding of the berberine; (iii) very small increases in duplex melting temperature in the presence of the berberine. Our results reveal that substitution of a hydroxyl group to a methoxy group on the 19-position, thereby converting the berberrubine to the berberine is associated with a non-specific DNA binding affinity and a reduced topoisomerase II poisoning. The presence of a bulky 19-methoxy substituent decreases intercalating properties of berberine and makes it inactive as topoisomerase II poison.

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