Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives.

摘要: A small series of five novel berberine derivatives was synthesized by the Cu-catalyzed click reaction 9-propargyladenine with 9-O-(azidoalkyl)berberine derivatives. The association resulting berberine-adenine conjugates representative quadruplex-forming oligonucleotides 22AG dA(G3TTA)3G3 and a2 d(ACAG4TGTG4)2 examined photometric fluorimetric titrations, thermal DNA denaturation analysis, CD spectroscopy. results from spectrometric titrations indicated formation 2:1 or 1:1 complexes (ligand:G4-DNA) log Kb values 10-11 (2:1) 5-6 (1:1), which are typical for Notably, a clear relationship between binding affinity ligands length alkyl linker chain, n, not observed. However, depending on structure, exhibited different effects when bound to G4-DNA, such as fluorescent light-up ICD bands, mostly pronounced n = 4 (with a2) 5 22AG), thus indicating that each ligand-G4-DNA complex has specific structure respect relative alignment conformational flexibility ligand in site. It shown exemplarily one exhibit selective binding, specifically selectivity quadruplex competition duplex DNA, preferential stabilization G4-DNA forms KRAS. experimental data do provide evidence significant effect adenine unit ligands, example, additional loops, presumably because residue is sterically shielded neighboring triazole unit.