Spacer length and attaching position-dependent binding of synthesized protoberberine dimers to double-stranded DNA

Six jatrorrhizine homodimers and berberine–jatrorrhizine heterodimers have been synthesized in moderate to good yields from the reaction of jatrorrhizine with α,ω-dibromoalkanes and 9-O-(ω-bromoalkyl)berberines, respectively. Their binding activities toward calf thymus (CT) DNA and three double-stranded oligodeoxynucleotides, d(AAGAATTCTT)2, d(TAAGAATTCTTA)2, and d(TTAAGAATTCTTAA)2, were investigated by means of spectrofluorimetric and spectrophotometric titrations. The results indicate that these dimers exhibit enhanced DNA-binding affinities due to the cooperative interaction of the two protoberberine subunits. A comparative study of the DNA-binding behaviors of berberine homodimers, jatrorrhizine homodimers, and berberine–jatrorrhizine heterodimers suggests that spacer length and attaching position are of great importance in modulating their DNA-binding affinities.

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