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G quadruplex

Ye Teng, Smritimoy Pramanik, Hisae Tateishi-Karimata, Tatsuya Ohyama, Naoki Sugimoto
The trinucleotide repeat d(CXG) (X = A, C, G or T) is the most common sequence causing repeat expansion disorders. The formation of non-canonical structures, such as hairpin structures with X-X mismatches, has been proposed to affect gene expression and regulation, which are important in pathological studies of these devastating neurological diseases. However, little information is available regarding the thermodynamics of the repeat sequence under crowded cellular conditions where many non-canonical structures such as G-quadruplexes are highly stabilized, while duplexes are destabilised...
January 12, 2018: Biochemical and Biophysical Research Communications
Haiyin Li, Jiafu Chang, Panpan Gai, Feng Li
Fluorescence biosensing strategy has drawn substantial attention due to their advantages of simplicity, convenience, sensitivity and selectivity, but unsatisfactory structure stability, low fluorescence quantum yield, high cost of labeling, and strict reaction conditions associated with current fluorescence methods severely prohibit their potential application. To address these challenges, we herein propose an ultrasensitive label-free fluorescence biosensor by integrating hemin/G-quadruplex-catalyzed oxidation reaction with aggregation induced emission (AIE) fluorogen-based system...
January 16, 2018: ACS Applied Materials & Interfaces
Ruibo Zhong, Mingshu Xiao, Changfeng Zhu, Xizhong Shen, Qian Tang, Weijia Zhang, Lihua Wang, Shiping Song, Xiangmeng Qu, Hao Pei, Cheng Wang, Li Li
By incorporating hemin into G-quadruplex (G4) during cation-templated self-assembly between guanosine and KB(OH)4, we have constructed an artificial enzyme hydrogel (AEH)-based system for the highly sensitive and selective detection of Pb2+. The sensing strategy is based on a Pb2+-induced decrease in AEH activity. Due to the higher efficiency of Pb2+ for stabilizing G4 compared with K+, the Pb2+ ions substitute K+ and trigger hemin release from G4, thus giving rise to a conformational interconversion accompanied by the loss of enzyme activity...
January 16, 2018: ACS Applied Materials & Interfaces
Lei He, Zhenyu Meng, Dechen Xu, Fangwei Shao
G-quadruplexes (GQ) folded by the oncogenic G-rich sequences are the promising targets for developing anticancer therapeutic molecules. However, the current drug development mainly focused on non-covalent dynamic binders to stabilize GQ structures, while the covalent targeting from inorganic complexes via chelating principles, as a potent therapeutic strategy was surprisingly lack of exploration. Herein, a series of dinuclear platinum complexes, [(Pt(Dip)Cl)2(μ-diamine)](NO3)2 (Dip: 4,7-diphenyl-1,10-phenanthroline), were designed to contain two dual-functional Pt cores connected by an alkyl linkage...
January 15, 2018: Scientific Reports
Valeria Romanucci, Armando Zarrelli, Sandra Liekens, Sam Noppen, Christophe Pannecouque, Giovanni Di Fabio
The biological relevance of tetramolecular G-quadruplexes especially as anti-HIV agents has been extensively reported in the literature over the last years. In the light of our recent results regarding the slow G-quadruplex folding kinetics of ODNs based on d(TGGGAG) sequence, here we report a systematic anti-HIV screening to investigate the impact of the G-quadruplex folding on their anti-HIV activity. In particular, varying the single stranded concentrations of ODNs, it has been tested a pool of ODN sample solutions with different G-quadruplex concentrations...
January 5, 2018: European Journal of Medicinal Chemistry
Zu-Zhuang Wei, Qi-Pin Qin, Ting Meng, Cai-Xing Deng, Hong Liang, Zhen-Feng Chen
Two platinum(II) complexes [Pt(L)(DMSO)Cl] (1) and [Pt(L)(pn)]Cl (2) with 5-bromo-oxoisoaporphine (H-L) were synthesized. We found that the two new platinum(II) complexes were more selective for Hep-G2 tumor cells than for normal cells (HL-7702, WI-38 and L-o2 cell lines). 5-Bromine-oxoisoaporphine platinum(II) complex 2 was a telomerase inhibitor targeting c-myc G4, and it triggered Hep-G2 cell apoptosis more potently than complex 1. Moreover, they induced cell apoptosis via disruption of mitochondrial functions...
January 4, 2018: European Journal of Medicinal Chemistry
Bertrand Benoît, Maria A O'Connell, Zöe A E Waller, Manfred Bochmann
Cyclometalated (C^N^C)Au(III) complexes bearing functionalized N-heterocyclic carbene (NHC) ligands provide a high-yielding, modular route to bioconjugated and binuclear complexes. That methodology has been applied to the synthesis of bioconjugated complexes presenting biotin and 17α-ethynylestradiol vectors, as well as to the synthesis of bimetallic Au(III)/Au(I) complexes. The in vitro antiproliferative activities of these compounds against various cancer cells lines depend on the linker length, with the longer linker being the most potent...
January 15, 2018: Chemistry: a European Journal
Shangdong Guo, Hong Lu
Hepatocyte nuclear factor 4-alpha (HNF4α) is a well-established master regulator of liver development and function. Restoration of HNF4α can treat multiple liver disorders and liver cancers. To date, HNF4α is still "undruggable" due to lack of known activating ligands. Thus, understanding the regulatory mechanism of HNF4α expression may help develop an alternative approach to modulate HNF4α protein levels. G-quadruplexes (G4) are non-canonical stable secondary structures discovered mostly in the promoters of oncogenes...
January 13, 2018: Molecular and Cellular Biochemistry
Efres Belmonte-Reche, Marta Martínez-García, Aurore Guédin, Michela Zuffo, Matilde Arévalo-Ruiz, Filippo Doria, Jenny Campos-Salinas, Marjorie Maynadier, Jose-Juan Lopez-Rubio, Mauro Freccero, Jean-Louis Mergny, Jose María Perez-Victoria, Juan Carlos Morales
G-quadruplexes (G4) are DNA secondary structures which take part in the regulation of gene expression. Putative G4 forming sequences (PQS) have been reported in mammals, yeast, bacteria and viruses. Here, we present PQS searches on the genomes of T. brucei, L. major and P. falciparum. We found telomeric sequences and new PQS motifs. Biophysical experiments showed that EBR1, a 29 nucleotide long highly repeated PQS in T. brucei, forms a stable G4 structure. G4 ligands based on carbohydrate conjugated naphthalene diimides (carb-NDIs) which bind G4's including hTel, could bind EBR1 with selectivity versus dsDNA...
January 11, 2018: Journal of Medicinal Chemistry
Aaron M Fleming, Judy Zhu, Yun Ding, Joshua A Visser, Julia Zhu, Cynthia J Burrows
The cellular response to oxidative stress includes transcriptional changes, particularly for genes involved in DNA repair. Recently, our laboratory demonstrated that oxidation of 2`-deoxyguanosine (G) to 8-oxo-7,8-dihydro-2`-deoxyguanosine (OG) in G-rich potential G-quadruplex sequences (PQSs) in gene promoters impacts the level of gene expression up or down depending on the position of the PQS in the promoter. In the present report, bioinformatic analysis found that the 390 human DNA repair genes in the genome ontology initiative harbor 2,936 PQSs in their promoters and 5`-untranslated regions (5`-UTRs)...
January 10, 2018: Biochemistry
Lynne M Harris, Katelyn R Monsell, Florian Noulin, M Toyin Famodimu, Nicolas Smargiasso, Christian Damblon, Paul Horrocks, Catherine J Merrick
G-quadruplexes are DNA or RNA secondary structures that can be formed from guanine-rich nucleic acids. These four-stranded structures, composed of stacked quartets of guanine bases, can be highly stable and have been demonstrated to occur in vivo in the DNA of human cells and other systems, where they play important biological roles, influencing processes such as telomere maintenance, DNA replication and transcription, or in the case of RNA G-quadruplexes, RNA translation and processing. We report for the first time that DNA G-quadruplexes can be detected in the nuclei of the malaria parasite Plasmodium falciparum, which has one of the most A/T-biased genomes sequenced and therefore possesses few guanine-rich sequences with the potential to form G-quadruplexes...
January 8, 2018: Antimicrobial Agents and Chemotherapy
Jing Zhu, Qijie Hao, Yi Liu, Zhaohui Guo, Buayxigul Rustam, Wei Jiang
The detection of uracil-DNA glycosylase (UDG) activity is pivotal for its biochemical studies and the development of drugs for UDG-related diseases. Here, we explored an integrated DNA structure switch for high sensitive detection of UDG activity. The DNA structure switch containing two branched hairpins was employed to recognize UDG enzyme and generate fluorescent signal. Under the action of UDG, one branched hairpin was impelled folding into a close conformation after the excision of the single uracil. This reconfigured hairpin could immediately initiate the polymerization/nicking amplification reaction of another branched hairpin accompanying with the release of numerous G-quadruplexes (G4s)...
March 1, 2018: Talanta
Yuhang Wu, Hong Zhang, Junfeng Xiang, Zhihua Mao, Gang Shen, Fengmin Yang, Yan Liu, Wei Wang, Ning Du, Jinghua Zhang, Yalin Tang
Lung cancer is the leading cause of cancer-related deaths worldwide, and approximately 85% are diagnosed as non-small-cell lung cancer (NSCLC). However, efficient detection and diagnosis of NSCLC at early stage is still challenging. In this work, we developed a simple, ultrasensitive and high selective strategy for A549 human NSCLC cells detection based on combining the reorganization property of a novel cyanine dye 3,3'-di(3-sulfopropyl)-4,5,4',5'-dibenzo-9-methyl-thiacarbocyanine triethylammonium salt (cy-M) to aptamer S6 G-quadruplex structure having specific affinity to NSCLC cells, which induced a dramatic fluorescence enhancement (~ 104 times)...
March 1, 2018: Talanta
Li-Ping Jia, Li-Juan Wang, Rong-Na Ma, Lei Shang, Wei Zhang, Qing-Wang Xue, Huai-Sheng Wang
In the present work a highly sensitive and selective aptasensor was developed for the determination of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) based on the hybridization chain reaction (HCR) signal amplification. It was observed that the aptamer of 8-OH-dG could hybridize with the capture DNA immobilized on the gold electrode with a sticky tail left, which initiated the HCR and led to the formation of extended dsDNA structure on the electrode surface. Then the electroactive species ([Ru(NH3)6]3+, RuHex) intercalated into the dsDNA grooves to generate the amplified signal...
March 1, 2018: Talanta
Wei Tan, Long Yi, Zhentao Zhu, Lulu Zhang, Jiang Zhou, Gu Yuan
A guanine-rich human mature microRNA, miR-1587, was discovered to form stable intramolecular G-quadruplexes in the presence of K+, Na+ and low concentration of NH4+ (25mM) by electrospray ionization mass spectrometry (ESI-MS) combined with circular dichroism (CD) spectroscopy. Furthermore, under high concentration of NH4+ (100mM) or molecular crowding environments, miR-1587 formed a dimeric G-quadruplex through 3'-to-3' stacking of two monomeric G-quadruplex subunits with one ammonium ion sandwiched between the interfaces...
March 1, 2018: Talanta
Kaili Zhang, Lei Wang, Haiyan Zhao, Wei Jiang
Transcription factors (TFs) play central roles in the regulation of gene expression by binding with specific DNA sequences. As a potential diagnostic marker, sensitive detection of TFs is essential for pharmacological research development and clinical disease diagnosis. Here, a new fluorescent method based on target binding protection mediated rolling circle amplification (RCA) was developed for TFs detection. A hairpin probe with recognition site for target binding, cleavage site for Nt.BbvCI digestion and two hanging DNA strands with part of G-quadruplex complementary sequences for signal output was designed...
March 1, 2018: Talanta
Sweta Tripathi, Ritu Barthwal
Interaction of mitoxantrone (MTX) with G-quadruplex, leading to inhibition of telomerase enzyme and anticancer action, is not understood. Titrations of MTX with [d-(TTAGGGT)]4, comprising human telomere single repeat sequence, have been monitored by fluorescence and 1H/31PNMR spectroscopy. Binding induces chemical shift changes in GNH (~0.3ppm), T2/T7/A3 base protons and sequence specific shifts in 31P resonances. Absence of large downfield shifts in 31P signals and presence of all sequential NOEs show that classical intercalation of drug between base quartets does not occur...
January 5, 2018: International Journal of Biological Macromolecules
Yanwei Cao, Xiaoxuan Xiang, Renjun Pei, Yang Li, Yuting Yan, Xinhua Guo
A junction DNA nanostructure has been successfully built in lithium acetate buffer solution at a near-neutral pH value through the connection of two slipped junction structures that are formed by G-rich and C-rich strands. The GC-rich duplex junctions in the nanostructure can be switched to G-quadruplexes and i-motifs in weakly acidic potassium acetate solution, which leads to the assembly of DNA nanostructures composed of alternating quadruplex and duplex DNA structures. The transformation between different DNA nanoarchitectures may be applied to the operation of 'DNA nanomachines'...
December 2017: Royal Society Open Science
Cuiying Lin, Huixia Zheng, Mi Sun, Yajuan Guo, Fang Luo, Longhua Guo, Bin Qiu, Zhenyu Lin, Guonan Chen
A simple, low-cost, and sensitive liposome-based colorimetric aptasensor has been developed to detect ochratoxin A (OTA). Specifically, a dumbbell-shaped probe was designed, including magnetic beads (MBs), double-stranded DNA (dsDNA), and enzyme-encapsulated liposome. The dsDNA formed by the hybridization between OTA aptamer and its complementary probe. And the dsDNA was used to contact the MBs and the enzyme-encapsulated liposome. In the presence of OTA, the aptamer preferred to combine with OTA to form G-quadruplex, resulting in the release of the detection probe and the enzyme-encapsulated liposome...
March 9, 2018: Analytica Chimica Acta
Rabindra Nath Das, Edith Chevret, Vanessa Desplat, Sandra Rubio, Jean-Louis Mergny, Jean Guillon
G-quadruplexes (G4) are stacked non-canonical nucleic acid structures found in specific G-rich DNA or RNA sequences in the human genome. G4 structures are liable for various biological functions; transcription, translation, cell aging as well as diseases such as cancer. These structures are therefore considered as important targets for the development of anticancer agents. Small organic heterocyclic molecules are well known to target and stabilize G4 structures. In this article, we have designed and synthesized 2,6-di-(4-carbamoyl-2-quinolyl)pyridine derivatives and their ability to stabilize G4-structures have been determined through the FRET melting assay...
December 30, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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