868. Effect of Nucleic Acid Size on Physical Properties and Biological Activity of Redox-Responsive Polyplexes: Plasmid DNA vs. Antisense Oligonucleotides

Long-term high fat-carbohydrates diet (HF-CD) contributes to the formation of irreversible changes in the organism that lead to the emergence of civilization diseases. In this study, the impact of three-month high-fat diet on the physical properties of erythrocytes (RBCs) was studied. Furthermore, the biological activity of Cistus incanus L. extracts, plant known with high pro-health potential, in relation to normal and HF-CD RBCs, was determined. Obtained results have shown that, applied HF-CD modified shape, membrane potential and osmotic resistance of erythrocytes causing changes in membrane lipid composition and the distribution of lipids. The impact of HF-CD on physical properties of RBCs along with atherosclerotic lesions of the artery was visible, despite the lack of statistically significant changes in blood morphology and plasma lipid profile. This suggests that erythrocytes may be good markers of obesity-related diseases. The studies of biological activity of Cistus incanus L. extracts have demonstrated that they may ameliorate the effect of HF-CD on erythrocytes through the membrane-modifying and antioxidant activity.

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Physical properties, ligand substitution reactions, and biological activity of Co(iii)-Schiff base complexes

Dalton Transactions ◽

10.1039/c8dt04606a ◽

2019 ◽

Vol 48 (18) ◽

pp. 5987-6002 ◽

Cited By ~ 5

Author(s):

A. Paden King ◽

Hendryck A. Gellineau ◽

Samantha N. MacMillan ◽

Justin J. Wilson

Keyword(s):

Biological Activity ◽

Schiff Base ◽

Physical Properties ◽

Ligand Exchange ◽

Ligand Substitution ◽

Schiff Base Complexes ◽

Substitution Reactions ◽

Anticancer Properties ◽

Ligand Substitution Reactions

A subset of fluorinated Co(iii) Schiff base complexes was synthesized, and their structural, ligand exchange, and anticancer properties were investigated.

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Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.17.54 ◽

2021 ◽

Vol 17 ◽

pp. 622-629

Author(s):

Naohiro Horie ◽

Takao Yamaguchi ◽

Shinji Kumagai ◽

Satoshi Obika

Keyword(s):

Nucleic Acid ◽

Binding Affinity ◽

Antisense Oligonucleotides ◽

Modified Oligonucleotides ◽

Biophysical Properties ◽

Chemical Modifications ◽

Antisense Technology ◽

Strong Affinity ◽

The Stability

Chemical modifications have been extensively used for therapeutic oligonucleotides because they strongly enhance the stability against nucleases, binding affinity to the targets, and efficacy. We previously reported that oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing the thymine (T) nucleobase show excellent biophysical properties for applications in antisense technology. In this paper, we describe the synthesis of GuNA[Me] phosphoramidites bearing other typical nucleobases including adenine (A), guanine (G), and 5-methylcytosine (mC). The phosphoramidites were successfully incorporated into oligonucleotides following the method previously developed for the GuNA[Me]-T-modified oligonucleotides. The binding affinity of the oligonucleotides modified with GuNA[Me]-A, -G, or -mC toward the complementary single-stranded DNAs or RNAs was systematically evaluated. All of the GuNA[Me]-modified oligonucleotides were found to have a strong affinity for RNAs. These data indicate that GuNA[Me] could be a useful modification for therapeutic antisense oligonucleotides.

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Efficient Inhibition of SARS-CoV-2 Using Chimeric Antisense Oligonucleotides through RNase L Activation

10.1101/2021.03.04.433849 ◽

2021 ◽

Author(s):

Xiaoxuan Su ◽

Wenxiao Ma ◽

Boyang Cheng ◽

Qian Wang ◽

Zefeng Guo ◽

...

Keyword(s):

Nucleic Acid ◽

Antisense Oligonucleotides ◽

Target Recognition ◽

Vero Cells ◽

Rnase L ◽

Rna Targets ◽

Infection Models ◽

Antisense Sequence ◽

Innate Antiviral Response ◽

Chimeric Oligonucleotides

AbstractThere is an urgent need for effective antiviral drugs to alleviate the current COVID-19 pandemic. Here, we rationally designed and developed chimeric antisense oligonucleotides to degrade envelope and spike RNAs of SARS-CoV-2. Each oligonucleotide comprises a 3’ antisense sequence for target recognition and a 5’-phosphorylated 2’-5’ poly(A)4 for guided ribonuclease L (RNase L) activation. Since RNase L can potently cleave single strand RNA during innate antiviral response, the improved degradation efficiency of chimeric oligonucleotides was twice as much as classic antisense oligonucleotides in Vero cells, for both SARS-CoV-2 RNA targets. In pseudovirus infection models, one of chimeric oligonucleotides targeting spike RNA achieved potent and broad-spectrum inhibition of both SARS-CoV-2 and its recently reported N501Y and/or ΔH69/ΔV70 mutants. These results showed that the constructed chimeric oligonucleotides could efficiently degrade pathogenic RNA of SARS-CoV-2 facilitated by immune activation, showing promising potentials as antiviral nucleic acid drugs for COVID-19.

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Study on rapid screening technology of antisense oligonucleotides for SARS-CoV-2

10.21203/rs.3.rs-479520/v2 ◽

2021 ◽

Author(s):

Huawei Shen

Keyword(s):

Nucleic Acid ◽

Antisense Oligonucleotides ◽

Structural Characteristics ◽

Inhibitory Effect ◽

Rapid Screening ◽

Short Term ◽

Physical Isolation ◽

The World ◽

Actual Use ◽

Screening Technology

Abstract According to the structural characteristics of SARS-CoV-2 nucleic acid,SARS-CoV-2 genomes were virtually segmented.After comparing with human genome,44707 SARS-CoV-2 genomes and 26 primates' genomes, 19 antisense oligonucleotides sequences were selected.Experimental results show that the combined inhibitory effect reaches 100% . Significance statement：Currently, effective methods of controlling the spread of SARS-CoV-2 are very limited, only physical isolation and vaccination.Although physical isolation can achieve some short-term results, but can not fundamentally solve the problem of epidemic spread.The time between the development of a vaccine and its actual use is very long.It often happens that the vaccine is developed successfully, but the epidemic situation is beyond control.If a mutant strain emerges, it will take longer.I hope that the rapid screening technology of SARS-CoV-2 antisense oligonucleotides will light up new hope for the future of mankind and contribute oriental wisdom to the world.

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Versatile Redox-Responsive Polyplexes for the Delivery of Plasmid DNA, Messenger RNA, and CRISPR-Cas9 Genome-Editing Machinery

ACS Applied Materials & Interfaces ◽

10.1021/acsami.8b09642 ◽

2018 ◽

Vol 10 (38) ◽

pp. 31915-31927 ◽

Cited By ~ 12

Author(s):

Yuyuan Wang ◽

Ben Ma ◽

Amr A. Abdeen ◽

Guojun Chen ◽

Ruosen Xie ◽

...

Keyword(s):

Genome Editing ◽

Plasmid Dna ◽

Messenger Rna ◽

Redox Responsive

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Biological Activity, Physical Properties, and Toxicity

International Journal of Quantitative Structure-Property Relationships ◽

10.4018/ijqspr.2021070102 ◽

2021 ◽

Vol 6 (3) ◽

pp. 25-34

Author(s):

Ranita Pal ◽

Pratim Kumar Chattaraj

Keyword(s):

Molecular Structure ◽

Biological Activity ◽

Molecular Biology ◽

Drug Design ◽

Physical Properties ◽

Quantitative Structure Activity Relationship ◽

Molecular Properties ◽

Quantitative Structure ◽

Qsar Analysis ◽

Structure Activity

In the current pandemic-stricken world, quantitative structure-activity relationship (QSAR) analysis has become a necessity in the domain of molecular biology and drug design, realizing that it helps estimate properties and activities of a compound, without actually having to spend time and resources to synthesize it in the laboratory. Correlating the molecular structure of a compound with its activity depends on the choice of the descriptors, which becomes a difficult and confusing task when we have so many to choose from. In this mini-review, the authors delineate the importance of very simple and easy to compute descriptors in estimating various molecular properties/toxicity.

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