One Terminal Guanosine Flip of Intramolecular Parallel G‐Quadruplex: Catalytic Enhancement of G‐Quadruplex/Hemin DNAzymes

Abstract

Numerous studies have shown compellinge vidence that incorporation of an inversion of polarity site (IPS) in G-rich sequences can affect the topological and structural characteristics of G-quadruplexes(G4s). Herein, the influence of IPS on the formation of ap reviously studied intramolecular parallel G4 of d(G 3 TG 3 TG 3 TG 3)(TTT) and its stacked higher-order structures is explored. Insertiono f3 '-3' or 5'-5' IPS did not change the parallel folding pattern of TTT.H owever,b oth the speciesa nd position of the IPS in TTT have a significant impact on the G4 stability and end-stacking through the alteration of G4-G4 interfaces properties. The data demonstrate that one base flip in each terminal Gtetrad can stabilizep arallel G4s and facilitate intermolecular packing of monomeric G4s. Such modifications can also enhance the fluorescencea nd enzymatic performances by promoting interactions between parallel G4s with N-methyl mesoporphyrin IX (NMM) and hemin, respectively.

Development of Fluorescent Aptasensors Based on G-Quadruplex Quenching Ability for Ochratoxin A and Potassium Ions Detection

“…For the parallel G-quadruplex system, we explored the mechanism of fluorophore quenching by introducing hemin, one of the common G-quadruplex ligands which bind to the parallel G-quadruplex with strong affinity. The parallel G-quadruplex and hemin binding usually occurs at the 3′end of G-tetrad [ 29 ]. The principle of the verification process is shown in Scheme 2 C,D, and the results are shown in Figure 2 C,D.…”

Topology of DNA G-Quadruplexes Can Be Harnessed in Holliday Junction-Based DNA Suprastructures to Control and Optimize Their Biocatalytic Properties

“…It is now established that the topology of a GQ strongly influences its biocatalytic properties. , However, the factors that control GQ topology, including flanking tails, loops, and G-quartet modification, and the way they influence the catalytic performance of the resulting GQ/hemin DNAzymes is not yet fully understood. Over the past years, a series of rules have emerged: (1) a GQ that adopts a parallel topology (i.e., with all the strands oriented in the same direction) is more catalytically competent than a GQ with either a hybrid topology (i.e., with one strand pointing in the opposite direction to the three others) or an antiparallel topology (with two pairs of strands oriented in an opposite direction); − (2) the addition of flanking nucleotides (e.g., d­(CCC) at either 5′ or 3′ ends of GQs, d­(A) − or d­(TC) ,, at the 3′ end) enhances the catalytic properties of GQs; (3) the modification of the base composition of the middle loop − regulates the enzymatic activity of the resulting GQ; (4) the addition of either an extra GQ unit − or a substrate aptamer − also improves catalytic performance of the resulting constructs; and finally, (5) the chemical modifications of Gs , involved in the G-quartet were also found to affect the activity of DNAzymes. These studies highlight the key roles that the microenvironment of the hemin binding site plays on the performance of GQ DNAzymes.…”

Thrombin-Binding Aptamer with Inversion of Polarity Sites (IPS): Effect on DNAzyme Activity and Anticoagulant Properties

“…Cao and co-workers studied the effect of 3′ and 5′ deoxyadenosine caps on the activity of DNAzyme based on tetramolecular G-quadruplexes [ 28 ]. Analogues with inversion of polarity sites were also used for the modification of unimolecular G-quadruplexes, which translated into an enhancement of their catalytic activity [ 29 ]. Virgilio et al examined tetramolecular G-quadruplexes with 5′-5′ internal inversion of polarity sites and double 3′ external G-quartets to obtain thermally stable DNAzymes with enhanced peroxidase activity [ 30 ].…”