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DNA‐Binding Affinities and Sequence Specificities of Protoberberine Alkaloids and Their Demethylated Derivatives: A Comparative Study
Author(s) -
Qin Yong,
Chen WenHua,
Pang JiYan,
Zhao ZhongZhen,
Liu Liang,
Jiang ZhiHong
Publication year - 2007
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200790019
Subject(s) - palmatine , chemistry , ethidium bromide , affinities , dna , stereochemistry , berberine , jatrorrhizine , demethylation , intercalation (chemistry) , isoquinoline , alkaloid , binding affinities , biochemistry , receptor , organic chemistry , dna methylation , gene expression , gene
Berberrubine ( 1a ), jatrorubine ( 2a ), and palmatrubine ( 3a ) have been chemically prepared by partial demethylation of berberine ( 1 ), jatrorrhizine ( 2 ), and palmatine ( 3 ), respectively. Their interactions with calf thymus (CT) DNA, poly(dA‐dT)⋅poly(dA‐dT), poly(dG‐dC)⋅poly(dG‐dC), and eight AT‐rich 12‐mer double‐stranded DNAs have been investigated by means of competitive ethidium bromide (EB) displacement experiments. The results showed that DNA‐binding affinities of these protoberberine alkaloids have been significantly improved by partial demethylation, and that all of these alkaloids have the preferable binding affinities with AT‐rich DNA. Especially, the sequence specificities of DNA‐binding of demethylated derivatives 1a, 2a , and 3a had changed to a certain extent when compared with the parent alkaloids 1, 2 , and 3 , respectively. The binding mode of these alkaloids was further confirmed by UV spectroscopic titration experiments. All the compounds bind to double‐stranded DNA most probably via an intercalating mode.