端粒长度的维持在肿瘤细胞的永生化过程中起到至关重要的作用。约85%的人体肿瘤细胞通过端粒酶延伸端粒,从而获得持续的增殖能力。另外,15%的人体肿瘤细胞通过端粒替代延伸机制(alternative lengthening of telomeres,ALT)延伸端粒。这...端粒长度的维持在肿瘤细胞的永生化过程中起到至关重要的作用。约85%的人体肿瘤细胞通过端粒酶延伸端粒,从而获得持续的增殖能力。另外,15%的人体肿瘤细胞通过端粒替代延伸机制(alternative lengthening of telomeres,ALT)延伸端粒。这两种机制对于维持肿瘤细胞中端粒的长度具有同等重要的意义。人体端粒由富含鸟嘌呤(G)的DNA重复序列组成,该序列在特定的条件下可以形成G-四链体(G4)的结构。此结构的形成可以从根本上抑制端粒酶和ALT对端粒的延伸而达到抗肿瘤的目的。因此,人体端粒G4-DNA作为抗肿瘤靶点的研究是近年来抗肿瘤研究的重要前沿领域之一。该文重点综述人体端粒G4-DNA稳定剂研发的最新研究进展。展开更多
The interaction of double-stranded （ds） and G-quadruplex （G4） DNA with sulfonyl 5-fluorouracil derivatives （5-fluoro-l-（arylsulfonyl） pyrimidine-2,4 （1H,3H）-diones） was investigated in this research, in whic...The interaction of double-stranded （ds） and G-quadruplex （G4） DNA with sulfonyl 5-fluorouracil derivatives （5-fluoro-l-（arylsulfonyl） pyrimidine-2,4 （1H,3H）-diones） was investigated in this research, in which Au electrodes modified with ds-DNA or G4-DNAs were used as a working electrode. The investigation showed that the binding affinity with G4-DNA was significantly increased when 5-fluorouracil （5-FU） was modified with arylsulfonyl groups. The presence of strong electron-withdrawing groups on benzene sulfonyl 5-FU greatly enhanced the binding selectivity （kG4-DNA/kds-DNA）. Such results provided new insights into the potential connections between the chemical structure of drug candidates and their anticancer activities.展开更多
In this study, electrospray ionization mass spectrometry （ESI-MS） was used to investigate interaction of 21 flavonoids （10 aglycones and 11 glycosides） with the parallel quadruplex structure [d（TGGGGT）]4. Relati...In this study, electrospray ionization mass spectrometry （ESI-MS） was used to investigate interaction of 21 flavonoids （10 aglycones and 11 glycosides） with the parallel quadruplex structure [d（TGGGGT）]4. Relative binding affinities of flavonoids toward [d（TGGGGT）]4 were estimated based on the fraction of bound DNA. It was found that [d（TGGGGT）]4 showed a binding preference to the flavonoid glycosides over flavonoid aglycones. It was d duced that glycosylation played a key role for the [d（TGGGGT）]a-binding properties of flavonoid glycosides. Upon collision-induced dissociation, complexes of flavonoid/[d（TGGGGT）]4 underwent the loss of flavonoids, suggesting an end-stacking binding mode. The current work demonstrates that ESI-MS is a powerful tool in the study of irheraction between drugs and nucleic acids.展开更多
文摘端粒长度的维持在肿瘤细胞的永生化过程中起到至关重要的作用。约85%的人体肿瘤细胞通过端粒酶延伸端粒,从而获得持续的增殖能力。另外,15%的人体肿瘤细胞通过端粒替代延伸机制(alternative lengthening of telomeres,ALT)延伸端粒。这两种机制对于维持肿瘤细胞中端粒的长度具有同等重要的意义。人体端粒由富含鸟嘌呤(G)的DNA重复序列组成,该序列在特定的条件下可以形成G-四链体(G4)的结构。此结构的形成可以从根本上抑制端粒酶和ALT对端粒的延伸而达到抗肿瘤的目的。因此,人体端粒G4-DNA作为抗肿瘤靶点的研究是近年来抗肿瘤研究的重要前沿领域之一。该文重点综述人体端粒G4-DNA稳定剂研发的最新研究进展。
基金supported by the National Natural Science Foundation of China (21073133,20843007)Zhejiang Provincial Natural Science Foundation of China (Y4080177,Y4090248,Y5100283)Zhejiang Provincial Ministry of Education (Y200907715)
文摘The interaction of double-stranded （ds） and G-quadruplex （G4） DNA with sulfonyl 5-fluorouracil derivatives （5-fluoro-l-（arylsulfonyl） pyrimidine-2,4 （1H,3H）-diones） was investigated in this research, in which Au electrodes modified with ds-DNA or G4-DNAs were used as a working electrode. The investigation showed that the binding affinity with G4-DNA was significantly increased when 5-fluorouracil （5-FU） was modified with arylsulfonyl groups. The presence of strong electron-withdrawing groups on benzene sulfonyl 5-FU greatly enhanced the binding selectivity （kG4-DNA/kds-DNA）. Such results provided new insights into the potential connections between the chemical structure of drug candidates and their anticancer activities.
基金Acknowledgement This work was supported by the National Natural Science Foundation of China （No. 28073137）.
文摘In this study, electrospray ionization mass spectrometry （ESI-MS） was used to investigate interaction of 21 flavonoids （10 aglycones and 11 glycosides） with the parallel quadruplex structure [d（TGGGGT）]4. Relative binding affinities of flavonoids toward [d（TGGGGT）]4 were estimated based on the fraction of bound DNA. It was found that [d（TGGGGT）]4 showed a binding preference to the flavonoid glycosides over flavonoid aglycones. It was d duced that glycosylation played a key role for the [d（TGGGGT）]a-binding properties of flavonoid glycosides. Upon collision-induced dissociation, complexes of flavonoid/[d（TGGGGT）]4 underwent the loss of flavonoids, suggesting an end-stacking binding mode. The current work demonstrates that ESI-MS is a powerful tool in the study of irheraction between drugs and nucleic acids.
