旁侧序列对端粒DNA G-quadruplex热稳定性和折叠与去折叠动力学的影响

从热力学和动力学两个方面研究了旁侧序列对人端粒核心序列G3（T2AG3）3在钠离子溶液中所形成的Cr-quadruplex结构的影响．紫外吸收熔解实验表明G3（T2AG3）3一侧或两侧加上6个胸腺嘧啶核苷酸序列（T6）会明显降低G-quadruplex的相变温度（Tm）．在3′端加上T6时Tm降低约5℃，在5′端加上T6时Tm降低约10℃，两侧同时加上T6时L降低16℃．采用表面等离子体共振（surface plasmon resonance，SPR）测定G-quadruplex折叠和去折叠动力学的结果表明旁侧序列的加入同时降低了折叠和去折叠的速率常数（kf，ku），使折叠平衡常数（KF）由9．01降至7．44．上述结果表明旁侧序列的存在降低了G-quadruplex结构的稳定性．

Effect of Flanking Sequence on the Thermal Stability and Folding Kinetics of Telomere G-Quadruplex

The G-rich strand of human telomeric DNA can fold into a four-stranded structure called(G-quadruplex.)In this work,we studied the effect of flanking sequence on the thermal stability and the folding/unfolding kinetics of G-quadruplex formed by the core sequence G_(3)(T_(2)AG_(3))_(3) of human telomeric DNA.We show that the introduction of flanking sequence greatly reduced the thermal stability of G-quadruplex as exhibited by decreased melting temperature(T_(m)).On the other hand,the presence of flanking sequence also decreased the folding and unfolding rate constants(k_(f),k_(u)),resulting in a slightly decreased folding equilibrium constant(K_(F)).