新型咪唑并邻菲罗啉衍生物对人端粒G-四链体相对于双螺旋DNA的选择性识别

G-四链体DNA是抗肿瘤药物研究开发的重要靶点,选择性识别并稳定G-四链体DNA的化合物是潜在的抗肿瘤药物.文章利用紫外可见吸收滴定,荧光滴定,CD光谱以及荧光共振能量转移熔点实验(FRET-melring)研究了三个基于邻菲罗啉的新型衍生物(A,B和C)与人端粒G-四链体DNA的相互作用.结果表明三个化合物通过末端堆积方式与G四链体DNA相互作用,结合常数(K)约为106 mol-1·L.当浓度为3 μmol·L-1时,化合物A,B和C分别使G四链体DNA熔点温度增加(△Tm)16.2,10.5和10.9℃.而且在10倍过量双螺旋DNA存在下均能选择性识别并稳定G-四链体结构.

Selective Recognition on Human Telomeric G-quadruplex over Duplex DNAs by Novel Imidazophenanthroline Derivatives

G-quadruplex DNA is an important target for design of anticancer drugs,so the compounds selectively recognizing and stabilizing the structure of G-quadruplex DNA are the potential antitumor drugs.Here the interactions of three novel phenanthroline-based compounds A,B and C with human telomeric G-quadruplex DNA were studied by absorption titration,fluorescence titration,CD spectroscopy and FRET-melting methods.The results show that the three compounds bind to G-quadruplex DNA by end-stacking mode with the association constant(K) of about 106 mol-1·L.The compounds A,B and C can selectively recognize and stabilize G-quadruplex structure at level of 10-fold excess of duplex DNA,with the increase of the melting temperature(ΔTm) of 16.2,10.5 and 10.9 ℃ at 3 μmol·L-1 concentration,respectively.