scholarly journals Pressure Perturbation Studies of Noncanonical Viral Nucleic Acid Structures

Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1173
Author(s):  
Judit Somkuti ◽  
Orsolya Réka Molnár ◽  
Anna Grád ◽  
László Smeller

G-quadruplexes are noncanonical structures formed by guanine-rich sequences of the genome. They are found in crucial loci of the human genome, they take part in the regulation of important processes like cell proliferation and cell death. Much less is known about the subjects of this work, the viral G-quadruplexes. We have chosen three potentially G-quadruplex-forming sequences of hepatitis B. We measured the stability and the thermodynamic parameters of these quadruplexes. We also investigated the potential stabilization of these G-quadruplexes by binding a special ligand that was originally developed for cancer therapy. Fluorescence and infrared spectroscopic measurements were performed over wide temperature and pressure ranges. Our experiments indicate the small unfolding volume change of all three oligos. We found a difference between the unfolding of the 2-quartet and the 3-quartet G-quadruplexes. All three G-quadruplexes were stabilized by TMPyP4, which is a cationic porphyrin developed for stabilizing the human telomere.

RSC Advances ◽  
2016 ◽  
Vol 6 (16) ◽  
pp. 13080-13087 ◽  
Author(s):  
Li-Na Zhu ◽  
Shan Shi ◽  
Lin Yang ◽  
Min Zhang ◽  
Ke-Ke Liu ◽  
...  

A water soluble cationic porphyrin derivative TMPipEOPP can preferentially photocleave G-quadruplex in the presence of ​double-stranded DNA, thus might be used as a human telomere-targeted photosensitizer for tumor photodynamic therapy.


2019 ◽  
Vol 17 (4) ◽  
pp. 859-866
Author(s):  
Yoshiaki Masaki ◽  
Takeshi Inde ◽  
Atsuya Maruyama ◽  
Kohji Seio

To systematically determine the effect of N2-heteroaryl modification on the stability of G-quadruplex structures, six types of N2-heteroarylated deoxyguanosines were incorporated into oligonucleotides with intramolecular quadruplex-forming sequences obtained from the human telomere sequence.


Author(s):  
Morganna C. Lima ◽  
Elisa A. N. Azevedo ◽  
Clarice N. L. de Morais ◽  
Larissa I. O. de Sousa ◽  
Bruno M. Carvalho ◽  
...  

Background: Zika virus is an emerging arbovirus of global importance. ZIKV infection is associated with a range of neurological complications such as the Congenital Zika Syndrome and Guillain Barré Syndrome. Despite the magnitude of recent outbreaks, there is no specific therapy to prevent or to alleviate disease pathology. Objective: To investigate the role of P-MAPA immunomodulator in Zika-infected THP-1 cells. Methods: THP-1 cells were subjected at Zika virus infection (Multiplicity of Infection = 0.5) followed by treatment with P-MAPA for until 96 hours post-infection. After that, the cell death was analyzed by annexin+/ PI+ and caspase 3/ 7+ staining by flow cytometry. In addition, the virus replication and cell proliferation were accessed by RT-qPCR and Ki67 staining, respectively. Results: We demonstrate that P-MAPA in vitro treatment significantly reduces Zika virus-induced cell death and caspase-3/7 activation on THP-1 infected cells, albeit it has no role in virus replication and cell proliferation. Conclusions: Our study reveals that P-MAPA seems to be a satisfactory alternative to inhibits the effects of Zika virus infection in mammalian cells.


2019 ◽  
Vol 19 (5) ◽  
pp. 610-619 ◽  
Author(s):  
Xue-Qing Zhang ◽  
Lu-Ting Yu ◽  
Pei Du ◽  
Tian-Qi Yin ◽  
Zhi-Yuan Zhang ◽  
...  

Background:Regenerating islet-derived gene family member 4 (Reg4), a well-investigated growth factor in the regenerative pancreas, has recently been reported to be highly associated with a majority of gastrointestinal cancers. Pathological hyper-expression or artificial over-expression of Reg4 causes acceleration of tumor growth, migration, and resistance to chemotherapeutic 5-Fluorouracil (5-FU). Until now, no method has been successfully established for eliminating the effects of Reg4 protein.Methods:This study reports the production of an engineered immunoglobin, a single-chain variable fragment (scFv-Reg4), to specifically bind Reg4 and block the bioactivity. The complementary-determining regions (CDRs) against Reg4 were assigned using MOE and ZDOCK servers. The binding affinity (KD) was determined by bio-layer interferometry (BLI). MKN45 and AGS cell proliferation was determined by Thiazolyl blue tetrazolium bromide (MTT) method and the cell apoptosis was detected by flow cytometry assay.Results:The KD of scFv-Reg4 to Reg4 was determined to be 1.91×10-8. In MKN45 and AGS cell lines, scFv- Reg4 depressed Reg4-stimulated cell proliferation and the inhibitory rates were 27.7±1.5% and 17.3±2.6%, respectively. Furthermore, scFv significantly enhanced 5-FU-induced cell death, from 23.0±1.0% to 28.4±1.2% in MKN45 and 28.2±0.7% to 36.6±0.6% in AGS cells. Treatment with scFv alone could lyse cancer cells to a certain extent, but no significance has been observed.Conclusion:The single-chain antibody (scFv-Reg4) significantly inhibited gastric cancer cell proliferation and synergistically enhanced the lethal effect of 5-FU. Thus, traditional chemo-/radio- therapeutics supplemented with scFv-Reg4 may provide advances in the strategy for gastrointestinal cancer treatment.


2006 ◽  
Vol 13 (5) ◽  
pp. 191-193
Author(s):  
V. Sangwan ◽  
M. Park

Tight control of cell proliferation and morphogenesis in conjunction with programmed cell death (apoptosis) is required to ensure normal tissue patterning. [...]


2006 ◽  
Vol 94 (6) ◽  
pp. 776-780 ◽  
Author(s):  
H-W Hwang ◽  
J T Mendell

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Philipp Schult ◽  
Katrin Paeschke

AbstractDHX36 is a member of the DExD/H box helicase family, which comprises a large number of proteins involved in various cellular functions. Recently, the function of DHX36 in the regulation of G-quadruplexes (G4s) was demonstrated. G4s are alternative nucleic acid structures, which influence many cellular pathways on a transcriptional and post-transcriptional level. In this review we provide an overview of the current knowledge about DHX36 structure, substrate specificity, and mechanism of action based on the available models and crystal structures. Moreover, we outline its multiple functions in cellular homeostasis, immunity, and disease. Finally, we discuss the open questions and provide potential directions for future research.


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