The promoter region of proto-oncogene has continuous guanine-rich regions I–V, which form G-quadruplex (G4) structures. Reported RET20T G4 in the regions II–V has parallel folding in potassium-ion solutions; however, this G4-DNA is not an ideal drug target, as its formation is limited to a low concentration potassium-ion solution. Here, we demonstrate that RET-21mer in the regions I–IV forms a mixed parallel/anti-parallel G4 in either 50 mM K or 100 mM Na solutions. It is stable, with a melting temperature of 74.3°C in 100 mM Na solution and 91.2°C in 100 mM K solution. A loop forms a special G⋅G base-pair plane in K solution or an unconventional A⋅G⋅G plane in Na solution, stacking with the 3′ end G tetrad, stabilizing its conformation. We also show that RET-21mer G4 could exist under physiological conditions. Therefore, RET-21mer G4s are likely a major G4-DNA, providing a research direction for anti-cancer drug screening.

中文翻译：

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生理溶液条件下癌基因RET启动子区形成稳定的G四链体

原癌基因的启动子区具有连续的富含鸟嘌呤的区域I-V，形成G-四联体（G4）结构。报道的 RET20T G4 在 II-V 区在钾离子溶液中具有平行折叠；然而，这种 G4-DNA 并不是理想的药物靶点，因为它的形成仅限于低浓度的钾离子溶液。在这里，我们证明 I–IV 区域中的 RET-21mer 在 50 mM K 或 100 mM Na 溶液中形成混合平行/反平行 G4。它很稳定，在 100 mM Na 溶液中的熔化温度为 74.3°C，在 100 mM K 溶液中的熔化温度为 91.2°C。环在K溶液中形成特殊的G⋅G碱基对平面或在Na溶液中形成非常规的A⋅G⋅G平面，与3′端G四分体堆叠，稳定其构象。我们还表明 RET-21mer G4 可以在生理条件下存在。因此，RET-21mer G4s很可能是一种主要的G4-DNA，为抗癌药物筛选提供了研究方向。