quadruplex structure
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2021 ◽  
Vol 14 (12) ◽  
pp. 1326
Author(s):  
Weronika Kotkowiak ◽  
Zofia Jahnz-Wechmann ◽  
Anna Pasternak

Aptamers constitute an answer for the growing need for targeted therapy development. One of the most well-known representatives of this group of compounds is thrombin binding aptamers (TBA) targeted towards thrombin. The TBA inhibitory activity is determined by its spatial arrangement, which consists of two G-tetrads linked by two shorter TT loops and one longer TGT loop and folds into a unimolecular, antiparallel G-quadruplex structure. Interesting properties of the aptamer can be further improved via the introduction of a number of chemical modifications. Herein, a comprehensive analysis of the influence of pyrrolo-2’-deoxycytidine (Py-dC) and its derivatives on TBA physicochemical and biological properties has been presented. The studies have shown that the presence of modified residues at the T7 position of the TGT loop has only minor effects on TBA thermodynamic stability without affecting its folding topology. All analyzed oligomers exhibit anticoagulant properties, but only aptamer modified with a decyl derivative of Py-dC was able to inhibit thrombin activity more efficiently than unmodified, parental compounds. Importantly, the same compound also possessed the potential to effectively restrain HeLa cell line growth.


Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6595
Author(s):  
Peter Jonas Wickhorst ◽  
Heiko Ihmels ◽  
Thomas Paululat

Recently, several quadruplex-DNA-forming sequences have been identified in the insulin-linked polymorphic region (ILPR), which is a guanine-rich oligonucleotide sequence in the promoter region of insulin. The formation of this non-canonical quadruplex DNA (G4-DNA) has been shown to be involved in the biological activity of the ILPR, specifically with regard to its interplay with insulin. In this context, this contribution reports on the investigation of the association of the quadruplex-forming ILPR sequence a2 with insulin as well as with the well-known G4-DNA ligand 3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium (1), also named RHPS4, by optical and NMR spectroscopy. CD- and NMR-spectroscopic measurements confirmed the preferential formation of an antiparallel quadruplex structure of a2 with four stacked guanine quartets. Furthermore, ligand 1 has high affinity toward a2 and binds by terminal π stacking to the G1–G11–G15–G25 quartet. In addition, the spectroscopic studies pointed to an association of insulin to the deoxyribose backbone of the loops of a2.


2021 ◽  
Vol 22 (19) ◽  
pp. 10716
Author(s):  
Lulu Zhang ◽  
Jiang Zhou ◽  
Ming Xu ◽  
Gu Yuan

Hsa-miR-1587 has been found to be capable of forming G-quadruplex structures and is overexpressed in multiple cancer cell lines. Here, we explored the interactions between miR-1587 and proteins. HuProt™ human proteome microarray was utilized to screen the binding proteins, and it was discovered that CASK could bind to miR-1587 on the base of the G-quadruplex structure. Moreover, reelin and p21, which are downstream of CASK, were downregulated both transcriptionally and translationally by miR-1587, uncovered by q-RT-PCR and Western blot assays. Bioinformatic analysis was performed on STRING and Panther platforms, leading to the discovery that miR-1587 may be involved in intracellular metabolic and transcriptional physiological processes. This study explores the interaction of hsa-miR-1587 with proteins and provides a new strategy for the regulation of G-rich microRNA’s function.


Nanomaterials ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2280
Author(s):  
Hong Phan T. Nguyen ◽  
Thanihaichelvan Murugathas ◽  
Natalie O. V. Plank

Carbon nanotube field effect transistor (CNT FET) aptasensors have been investigated for the detection of adenosine using two different aptamer sequences, a 35-mer and a 27-mer. We found limits of detection for adenosine of 100 pM and 320 nM for the 35-mer and 27-mer aptamers, with dissociation constants of 1.2 nM and 160 nM, respectively. Upon analyte recognition the 35-mer adenosine aptamer adopts a compact G-quadruplex structure while the 27-mer adenosine aptamer changes to a folded duplex. Using the CNT FET aptasensor platform adenosine could be detected with high sensitivity over the range of 100 pM to 10 µM, highlighting the suitability of the CNT FET aptasensor platform for high performance adenosine detection. The aptamer restructuring format is critical for high sensitivity with the G-quadraplex aptasensor having a 130-fold smaller dissociation constant than the duplex forming aptasensor.


2021 ◽  
Vol 19 (13) ◽  
pp. 2891-2894
Author(s):  
Kazumitsu Onizuka ◽  
Erchissaran Ganbold ◽  
Yue Ma ◽  
Shogo Sasaki ◽  
Madoka E. Hazemi ◽  
...  

We achieve selective alkylation of parallel G-quadruplex DNA using a conjugate of a macrocyclic hexaoxazole and a sulfoxide precursor to a vinyl-quinazolinone.


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