设计合成了3个多胺取代的小檗碱衍生物5a～5c,并利用圆二色(CD)光谱、荧光共振能量转移(FRET)熔点实验、荧光光谱和聚合酶链反应(PCR)终止实验等手段研究了小檗碱衍生物5a～5c与端粒DNA的相互作用.结果表明,小檗碱衍生物5a～5c可以诱导端粒DNA序列形成反平行结构G-四链体,显著地提高了端粒G-四链体的稳定性,有效地抑制了端粒的扩增；而与双链DNA的相互作用则很小,是高选择性的端粒G-四链体配体.%A series of 9-O-substituted berberine derivatives (5a—5c) as telomeric quadruplex ligands was synthesized and evaluated. The interaction of berberine derivatives with telomeric G-quadruplex DNA was examined by CD spectroscopy, FRET-melting method, fluorescence titration assay and PCR-stop assay. The CD results indicated the derivatives were capable of inducing the formation of antiparallel G-quadruplex and the results from FRET-melting method clearly showed that derivatives with polyamine chain had high binding affinity and superior selectivity for telomeric G-quadruplex DNA over duplex. The PCR-stop assay results exhibited the inhibitory effect on the hybridization. All the results suggested the 9-O-substituted berberine derivatives were highly selective telomeric G-quadruplex DNA stabilizing ligands.
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