Synthesis, Crystal Structure and Interactions with different G-quadruplex DNA and ctDNA of Zn-CAP

来源 :The 12th International Symposium on Applied Biological Chemi | 被引量 : 0次 | 上传用户:kang573
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  In recent years,in order to improve the selectivity and reduce the side effects of DNA-targeting drugs,researchers have focused on finding molecules targeting on G-quadruplex DNA.In this study,one mononuclear zinc (Ⅱ) complex with 1,2-bis (5-chlorosalicylidene amino)-phenylene (CAP): C22C13N203.52n1.5H0.125 (Zn-CAP) was synthesized.The binding properties of Zn-CAP with G-quadruplex DNA and ctDNA were examined by Fluorescence,CD spectroscopic and FRET assay.In the Fluorescence emission spectral analysis,in the presence of K+,the addition of three series of G-quadruplex DNA (G4-HTG21,G4-Pu27 and G4-c-kit-1) into the Zn-CAP solution induced moderate or add hypochromicity with total quenching ratios of 10.73%,15.07% and 8.59% were achieved,respectively.While the addition of ctDNA under same condition only caused 7.08% quenching on the fluorescence emission of Zn-CAP.In the CD spectral analysis,the interaction with Zn-CAP could induce significant spectral changes on the CD absorption of G4-HTG21,G4-Pu27 and G4-c-kit-1,with 106.00%,93.06%,113.47% increment at 232 nm absorption,along with a 81.11%,92.80%,83.72% decrement at 295 nm or 270nm absorption,which demonstrated the antiparallel structure of G-quadruplex DNA are more stable in the presence of Zn-CAP.Comparatively,the addition of Zn-CAP could induce significant spectral changes on the CD absorption of double helix ctDNA,with 64.17% decrement on the positive peak absorption,along with a 90.91% increment on the negative peak absorption.On the other hand,in the FRET-melting assay analysis,it was clear that Zn-CAP at 0.5 equivalences could raise the melting temperature of G-quadruplex (F21T or FPu18T) by 3.45 ℃ and 15.85 ℃,indicated an obvious stabilization effect of Zn-CAP on G-quadruplex in Pu27.A11 the results indicated that Zn-CAP exhibited higher binding affinity and binding intensity to G-quadruplex DNA than ctDNA,especially G-quadruplex Pu27.
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