高选择性端粒G-四链体稳定性配体:9-O-多胺取代小檗碱衍生物的合成及活性评价

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.

Synthesis and Activity Evaluation of 9-O-Substituted Berberine Derivatives Containing Polyamine Chain as Highly Selective Telomeric G-Quadruplex Stabilizing Ligands

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.