Engineering of interlocked DNA G-quadruplexes as a robust scaffold

Abstract

Interlock is a structural element in DNA G-quadruplexes that can be compared with the commonly used complementary binding of ‘sticky ends’ in DNA duplexes. G-quadruplex interlocking can be a basis for the assembly of higher-order structures. In this study, we formulated a rule to engineer (3 + 1) interlocked dimeric G-quadruplexes and established the folding topology of the designed DNA sequences by nuclear magnetic resonance spectroscopy. These interlocked G-quadruplexes are very stable and can serve as compact robust scaffolds for various applications. Different structural elements can be engineered in these robust scaffolds. We demonstrated the anti-HIV inhibition activity of the newly designed DNA sequences.

Polymorphism of G4 associates: from stacks to wires via interlocks

“…Another known route for programming G4 association exploits interlocking via ‘sticky ends’, such as G/GC overhangs and vacancies. Guided head-to-head dimerization (scheme (d) in Figure 1 ) was first described for the so-called ‘3+1’ intramolecular structures with single-G overhangs and single vacancies in 5′-terminal tetrads ( 19 ). Programming head-to-tail interlocking, which is analogous to strand arrangement in ‘classical’ G-wires ( 20 , 21 ), seems to be more challenging than head-to-head dimerization.…”

G‐Quadruplex Structures and Their Interaction Diversity with Ligands

“…The remaining G-tetrad at the interface between the two monomers adopted an anti-anti-anti-syn align-ment, which contained three guanines from one monomer and one guanine from another monomer (in a "3+1" type). Likewise, the designed d(G 4 TG 2 TG 3 TG 3 T) and d(G 4 TG 3 TG 3 TG 2 T) sequences also formed interlocked G-quadruplexes [35] that were similar to the 93del d(G 4 TG 3 AG 2 AG 3 T) sequence ( Figure 4 e). These different interlocked dimeric G-quadruplexes are so stable that they can serve as compact robust scaffolds for many biological applications; for example, they can act as ligands that target the interfacial canyon of multimeric proteins.…”

Construction of nanostructures based on quadruplex DNA scaffolds

“…富G序列除了通过形成G-wires进行自组装方式外, Biyani和Nishigaki [47] 还基于d(G 11 T)序列形成的G-四链 体纳米结构, 提出了一种双分子G-四链体通过"堆积 木"进行组装的模型; 同样地, 一些特殊的富G序列通 过"互锁"的方式形成的双分子G-四链体, 包括93del为 主的3+1型-G-四链体结构的二聚, 同样为构建G-四链 超分子结构提供了可参考的组装模型 [48,49] .…”