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 alpha,omega-dibromoalkanes and 9-O-(omega-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. (c) 2006 Elsevier Ltd. All rights reserved.