Department of Chemistry and Konstanz Research School of Chemical Biology, University of Konstanz, 78467 Konstanz, Germany.
Bioorg Med Chem. 2013 Oct 15;21(20):6156-61. doi: 10.1016/j.bmc.2013.04.014. Epub 2013 Apr 16.
Guanosine-rich DNA sequences have the potential to adopt four-stranded conformations termed quadruplexes. The chromosomes of higher organisms are capped by so-called telomeres that are composed of repeats of the sequence TTAGGG. Up to 200 nucleotides of the G-rich strand form an overhang that is suspected to fold into intramolecular G-quadruplexes. Since induction of quadruplexes at the telomeres results in anti-proliferative effects, the intracellular structure of G-quadruplexes is of high interest as an anti-cancer drug target. Here we give a perspective on the elucidation of DNA sequence folds by electron paramagnetic resonance (EPR) distance measurements. The technique complements X-ray crystallography and NMR spectroscopy, as it can be applied in noncrystalline states, is not intrinsically limited by the size of the bio-macromolecular complex, and is able to analyze flexible structures or coexisting DNA conformation.
富含鸟嘌呤的 DNA 序列具有形成称为四链体的四链构象的潜力。高等生物的染色体由称为端粒的序列 TTAGGG 重复组成。富含 G 的链的长达 200 个核苷酸形成一个突出部分，据推测该部分会折叠成分子内 G-四链体。由于在端粒处诱导四链体导致抗增殖作用，因此 G-四链体的细胞内结构作为抗癌药物靶标受到高度关注。在这里，我们从电子顺磁共振（EPR）距离测量的角度来阐述 DNA 序列折叠。该技术补充了 X 射线晶体学和 NMR 光谱学，因为它可以应用于非晶态，不受生物大分子复合物大小的内在限制，并且能够分析灵活的结构或共存的 DNA 构象。
