Conformation of the telomeric DNA fragment dG₃(TTAG₃)₃ depends on multiple factors including solution conditions, length, and the nucleotide sequence of the flanking regions. In potassium solution, this sequence tends to adopt hybrid (3 + 1) G-quadruplex (G4) Form 1 or Form 2 conformation contingent on the flanking nucleotides. Theoretically, other (3 + 1) G4 folds (beyond Forms 1 and 2) are not sterically forbidden, but are presumably energetically disfavored. We report here on the effect of substituting the TTA loop with a single T nucleotide for one, two, or three loops of telomeric DNA that allowed us to expand the conformational diversity of the G4 DNA. Circular dichroism, gel migration, and chemical probing with DMS and ZnP1 (a porphyrin derivative sensitive to G4 conformation) were applied to monitor conformations that occurred upon shortening each loop to a single nucleotide. We found that all oligonucleotide models formed an intramolecular quadruplex structure and that shortening the loops led to the prevalence of G4 with quartets of the same polarity. Despite similar CD signatures, each modified sequence had one of three specific patterns of light-induced oxidation with ZnP1. According to the predominant modification pattern, folding of each sequence could be assigned to one of three major G4 conformations: parallel and two different (3 + 1) G4 folds. We here provide novel experimental evidence of the propensity for modified telomeric sequences to form a (3 + 1) G4 conformer containing one lateral and two propeller loops.

端粒DNA片段dG ₃（TTAG ₃）_3的构象取决于多种因素，包括溶液条件，长度和侧翼区域的核苷酸序列。在钾溶液中，该序列倾向于采用杂化（3 + 1）G-四链体（G4）1型或2型构象，视侧翼核苷酸而定。从理论上讲，其他（3 + 1）G4折叠（超出形式1和2）在空间上不是禁止的，但可能在能量上不利。我们在这里报告了用单个T核苷酸将TTA环替换为端粒DNA的一个，两个或三个环的作用，这使我们能够扩展G4 DNA的构象多样性。应用圆二色性，凝胶迁移和DMS和ZnP1（对G4构象敏感的卟啉衍生物）进行化学探测，以监测将每个环缩短为一个核苷酸后发生的构象。我们发现，所有寡核苷酸模型均形成分子内四链体结构，缩短环导致四极体具有相同极性的G4普遍存在。尽管CD签名相似，但每个修饰的序列均具有ZnP1光诱导氧化的三种特定模式之一。根据主要的修饰方式，可以将每个序列的折叠指定为三个主要G4构型之一：平行和两个不同的（3 +1）G4折叠。我们在这里提供新颖的实验证据，证明端粒修饰序列形成一个（3 +1）G4构象异构体的倾向，该构象异构体包含一个侧向和两个螺旋桨环。每个修饰的序列具有ZnP1光诱导氧化的三种特定模式之一。根据主要的修饰方式，可以将每个序列的折叠指定为三个主要G4构型之一：平行和两个不同的（3 +1）G4折叠。我们在这里提供新颖的实验证据，证明端粒修饰序列形成一个（3 +1）G4构象异构体的倾向，该构象异构体包含一个侧向和两个螺旋桨环。每个修饰的序列具有ZnP1光诱导氧化的三种特定模式之一。根据主要的修饰方式，可以将每个序列的折叠指定为三个主要G4构型之一：平行和两个不同的（3 +1）G4折叠。我们在这里提供新颖的实验证据，证明端粒修饰序列形成一个（3 +1）G4构象异构体的倾向，该构象异构体包含一个侧向和两个螺旋桨环。