scholarly journals Novel Lipid-Oligonucleotide Conjugates Containing Long-Chain Sulfonyl Phosphoramidate Groups: Synthesis and Biological Properties

2021 ◽  
Vol 11 (3) ◽  
pp. 1174
Author(s):  
Alina Derzhalova ◽  
Oleg Markov ◽  
Alesya Fokina ◽  
Yasuo Shiohama ◽  
Timofei Zatsepin ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Biological Properties ◽  
Dna And Rna ◽  
Guidance Molecules ◽  
Low Cytotoxicity ◽  
Oligonucleotide Conjugates ◽  
Long Chain

New lipid conjugates of DNA and RNA incorporating one to four [(4-dodecylphenyl)sulfonyl]phosphoramidate or (hexadecylsulfonyl)phosphoramidate groups at internucleotidic positions near the 3′ or 5′-end were synthesized and characterized. Low cytotoxicity of the conjugates and their ability to be taken up into cells without transfection agents were demonstrated. Lipid-conjugated siRNAs targeting repulsive guidance molecules a (RGMa) have shown a comparable gene silencing activity in PK-59 cells to unmodified control siRNA when delivered into the cells via Lipofectamine mediated transfection.

scholarly journals Design, Synthesis, and Molecular Docking Study of New Tyrosyl-DNA Phosphodiesterase 1 (TDP1) Inhibitors Combining Resin Acids and Adamantane Moieties

2021 ◽  
Vol 14 (5) ◽  
pp. 422
Author(s):  
Kseniya Kovaleva ◽  
Olga Yarovaya ◽  
Konstantin Ponomarev ◽  
Sergey Cheresiz ◽  
Amirhossein Azimirad ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Biological Properties ◽  
Glioma Cell Line ◽  
Resin Acids ◽  
Adamantane Derivatives ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Low Cytotoxicity ◽  
Covalent Intermediate

In this paper, a series of novel abietyl and dehydroabietyl ureas, thioureas, amides, and thioamides bearing adamantane moieties were designed, synthesized, and evaluated for their inhibitory activities against tyrosil-DNA-phosphodiesterase 1 (TDP1). The synthesized compounds were able to inhibit TDP1 at micromolar concentrations (0.19–2.3 µM) and demonstrated low cytotoxicity in the T98G glioma cell line. The effect of the terpene fragment, the linker structure, and the adamantane residue on the biological properties of the new compounds was investigated. Based on molecular docking results, we suppose that adamantane derivatives of resin acids bind to the TDP1 covalent intermediate, forming a hydrogen bond with Ser463 and hydrophobic contacts with the Phe259 and Trp590 residues and the oligonucleotide fragment of the substrate.

Recent Advances in the Cancer Bioimaging with Graphene Quantum Dots

2018 ◽  
Vol 25 (25) ◽  
pp. 2876-2893 ◽  
Author(s):  
Keheng Li ◽  
Xinna Zhao ◽  
Gang Wei ◽  
Zhiqiang Su
Keyword(s):  
Quantum Dots ◽  
Biomedical Applications ◽  
Cell Imaging ◽  
Graphene Quantum Dots ◽  
Biological Properties ◽  
Live Cells ◽  
Physical Chemical ◽  
Specific Cancer ◽  
Good Biocompatibility ◽  
Low Cytotoxicity

Fluorescent graphene quantum dots (GQDs) have attracted increasing interest in cancer bioimaging due to their stable photoluminescence (PL), high stability, low cytotoxicity, and good biocompatibility. In this review, we present the synthesis and chemical modification of GQDs firstly, and then introduce their unique physical, chemical, and biological properties like the absorption, PL, and cytotoxicity of GQDs. Finally and most importantly, the recent applications of GQDs in cancer bioimaging are demonstrated in detail, in which we focus on the biofunctionalization of GQDs for specific cancer cell imaging and real-time molecular imaging in live cells. We expect this work would provide valuable guides on the synthesis and modification of GQDs with adjustable properties for various biomedical applications in the future.

scholarly journals Synergistic effects between analogs of DNA and RNA improve the potency of siRNA-mediated gene silencing

2010 ◽  
Vol 38 (13) ◽  
pp. 4547-4557 ◽  
Author(s):  
Glen F. Deleavey ◽  
Jonathan K. Watts ◽  
Tommy Alain ◽  
Francis Robert ◽  
Anna Kalota ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Synergistic Effects ◽  
Dna And Rna

Defined pH-sensitive nanogels as gene delivery platform for siRNA mediated in vitro gene silencing

2017 ◽  
Vol 5 (11) ◽  
pp. 2328-2336 ◽  
Author(s):  
Mathias Dimde ◽  
Falko Neumann ◽  
Felix Reisbeck ◽  
Svenja Ehrmann ◽  
Jose Luis Cuellar-Camacho ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Gene Silencing ◽  
Transfection Efficiency ◽  
Genetic Material ◽  
Ph Sensitive ◽  
Carrier System ◽  
High Transfection Efficiency ◽  
Delivery Platform ◽  
Low Cytotoxicity

An advanced cationic carrier system which combines high transfection efficiency with low cytotoxicity and a control over the release of the encapsulated genetic material by the reduction of the multivalent architecture upon pH triggered degradation was developed.

Synthesis, physico-chemical and biological properties of DNA and RNA oligonucleotides containing short alkylamino internucleotide bond

2011 ◽  
Vol 76 (12) ◽  
pp. 1471-1486
Author(s):  
Milena Sobczak ◽  
Katarzyna Kubiak ◽  
Magdalena Janicka ◽  
Malgorzata Sierant ◽  
Barbara Mikolajczyk ◽  
...  
Keyword(s):  
Biological Properties ◽  
Protecting Group ◽  
Dna And Rna ◽  
Double Stranded Dna ◽  
Physico Chemical ◽  
Rna Oligomers ◽  
Phosphate Linkage ◽  
Sirna Molecule ◽  
Fetal Bovine ◽  
The Stability

The condensation of the 5′-O-DMT-3′-deoxy-3′-aminothymidine with 3′-O-TBDMS-thymidine- 5′-aldehyde, followed by reduction of the resultant imine derivative and removal of tert-butyldimethylsilyl (TBDMS) protecting group, provided a dimer (denoted as TNHT), which is a congener of dithymidine phosphate with the phosphate linkage 3′-O-P(O)(OH)-O-5′ replaced with an amino group (–NH–). After phosphitylation of the 3′-OH group, the dimer TNHT was introduced (by the standard phosphoramidite approach) into a central part of the nonadecathymidylate. This oligomer exhibited lower affinity to the complementary single and double stranded DNA complements as compared to unmodified T19 oligonucleotide. The cleavage of modified oligomer with the snake venom and calf spleen phosphodiesterases was completely suppressed at the site of modification. RNA oligomers containing the TNHT dimer were used for preparation of siRNA molecules directed towards mRNA of BACE1 (beta-site amyloid precursor protein cleaving enzyme). The presence of the TNHT units at the 3′-ends of the RNA strands of the siRNA molecule (the siRNA itself is an effective gene expression inhibitor for BACE1) preserved the gene silencing activity and improved the stability of the modified siRNA in 10% fetal bovine serum.

scholarly journals Design of the Oligonucleotide Carriers: Importance of Polyamine Chain Length

2018 ◽  
Author(s):  
Vadim V. Annenkov ◽  
Uma Maheswari Krishnan ◽  
Viktor A. Pal’shin ◽  
Stanislav N. Zelinskiy ◽  
Gayathri Kandasamy ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Silencing ◽  
Cancer Cells ◽  
Chain Length ◽  
Effective Interaction ◽  
Critical Length ◽  
Short Chain ◽  
Dna Oligonucleotides ◽  
Dna And Rna ◽  
Oligonucleotide Binding

Amine containing polymers are extensively studied as special carriers for short-chain RNA (13–25 nucleotides) which are applied as gene silencing agent in gene therapy of various diseases including cancer. Elaboration of the oligonucleotide carriers requires knowledge about peculiarities of oligonucleotide - polymeric amine interaction. Critical length of the interacting chains is the important parameter which allows to design sophisticated constructions containing oligonucleotide binding segments, solubilizing, protective and aiming parts. We studied interaction of (TCAG)n, n=1-6 DNA oligonucleotides with polyethylenimine and poly(N-(3-((3-(dimethyl­amino)propyl)(methyl)amino)propyl)-N-methylacrylamide). Critical length for oligonucleotides in interaction with polymeric amines is 8-12 units and complexation at these length can be accompanied by "all-or-nothing" effects. New dimethylacrylamide based polymers with grafted polyamine chains were obtained and studied in complexation with DNA and RNA oligonucleotides. The most effective interaction and transfection activity into A549 cancer cells was found for a sample with average number of nitrogens in polyamine chain equal to 27, i.e. for a sample in which all grafted chains are longer the critical length for polymeric amine - oligonucleotide complexation.

scholarly journals Sticky problems: extraction of nucleic acids from molluscs

2021 ◽  
Vol 376 (1825) ◽  
Author(s):  
Coen M. Adema
Keyword(s):  
Nucleic Acids ◽  
Dna Extraction ◽  
Extraction Methods ◽  
Biological Properties ◽  
Alternative Methods ◽  
28S Rrna ◽  
Future Directions ◽  
Dna And Rna ◽  
Standard Quality ◽  
Dna Extraction Methods

Traditional molecular methods and omics-techniques across molluscan taxonomy increasingly inform biology of Mollusca. Recovery of DNA and RNA for such studies is challenged by common biological properties of the highly diverse molluscs. Molluscan biomineralization, adhesive structures and mucus involve polyphenolic proteins and mucopolysaccharides that hinder DNA extraction or copurify to inhibit enzyme-catalysed molecular procedures. DNA extraction methods that employ the detergent hexadecyltrimethylammoniumbromide (CTAB) to remove these contaminants importantly facilitate molecular-level study of molluscs. Molluscan pigments may stain DNA samples and interfere with spectrophotometry, necessitating gel electrophoresis or fluorometry for accurate quantification. RNA can reliably be extracted but the ‘hidden break’ in 28S rRNA of molluscs (like most protostomes) causes 18S and 28S rRNA fragments to co-migrate electrophoretically. This challenges the standard quality control based on the ratio of 18S and 28S rRNA, developed for deuterostome animals. High-AT content in molluscan rRNA prevents the effective purification of polyadenylated mRNA. Awareness of these matters aids the continuous expansion of molecular malacology, enabling work also with museum specimens and next-generation sequencing, with the latter imposing unprecedented demands on DNA quality. Alternative methods to extract nucleic acids from molluscs are available from literature and, importantly, from communications with others who study the molecular biology of molluscs. This article is part of the Theo Murphy meeting issue ‘Molluscan genomics: broad insights and future directions for a neglected phylum’.

scholarly journals Characterization and Biological Properties of Zederone and Zedoarondiol from Rhizomes of En-Lueang (Curcuma cf. amada)

2018 ◽  
Vol 13 (12) ◽  
pp. 1934578X1801301 ◽  
Author(s):  
Songyot Anuchapreeda ◽  
Nattakanwadee Khumpirapang ◽  
Sawitree Chiampanichayakul ◽  
Wariya Nirachonkul ◽  
Aroonchai Saiai ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Antioxidant Properties ◽  
Biological Properties ◽  
Biologically Active ◽  
Total Phenolic ◽  
Peripheral Blood Mononuclear ◽  
Normal Peripheral Blood ◽  
Cytotoxicity Activity ◽  
Etoh Extract ◽  
Low Cytotoxicity

Curcuma cf. amada Roxb., also known as En-Lueang in Thailand, belongs to the Zingiberaceae family and grows from rhizomes. These rhizomes have been used in the Thai and Ayurveda systems of medicine. However, to our knowledge, no biologically active compounds isolated from En-Lueang have been reported. In this study, natural compounds were isolated from En-Lueang and their structures were determined by spectroscopic methods. The two isolated compounds were identified as zederone (1) and zedoarondiol (2) and their cytotoxicities against KG1a cells were investigated. The EtOH extract and EtOAc fraction showed stronger cytotoxic activity than n-hexane fraction against KG1a cells. In contrast, compound 1 showed strong cytotoxicity against KG1a cells, but low cytotoxicity toward normal peripheral blood mononuclear cells (PBMCs). Moreover, all the extracts and 1 had no effect on red blood cell hemolysis. The antioxidant properties of 1 were almost 2-fold higher than that of 2, in accordance with its total phenolic content of 8.8 mg/g, which is 2-fold higher than that of 2 (4.1 mg/g). In summary, two sesquiterpene compounds with leukemic cytotoxicity activity against the KG1a cell line were identified in En-Lueang extracts.

scholarly journals DNA interference: DNA-induced gene silencing in the appendicularian Oikopleura dioica

2015 ◽  
Vol 282 (1807) ◽  
pp. 20150435 ◽  
Author(s):  
Tatsuya Omotezako ◽  
Takeshi A. Onuma ◽  
Hiroki Nishida
Keyword(s):  
Gene Silencing ◽  
Fluorescent Proteins ◽  
Acetylcholinesterase Activity ◽  
Mrna Degradation ◽  
Coding Region ◽  
Oikopleura Dioica ◽  
Exogenous Dna ◽  
Dna And Rna ◽  
Double Stranded Dna ◽  
Pcr Products

RNA interference is widely employed as a gene-silencing system in eukaryotes for host defence against invading nucleic acids. In response to invading double-stranded RNA (dsRNA), mRNA is degraded in sequence-specific manner. So far, however, DNA interference (DNAi) has been reported only in plants, ciliates and archaea, and has not been explored in Metazoa. Here, we demonstrate that linear double-stranded DNA promotes both sequence-specific transcription blocking and mRNA degradation in developing embryos of the appendicularian Oikopleura dioica . Introduced polymerase chain reaction (PCR) products or linearized plasmids encoding Brachyury induced tail malformation and mRNA degradation. This malformation was also promoted by DNA fragments of the putative 5′-flanking region and intron without the coding region. PCR products encoding Zic-like1 and acetylcholine esterase also induced loss of sensory organ and muscle acetylcholinesterase activity, respectively. Co-injection of mRNA encoding EGFP and mCherry, and PCR products encoding these fluorescent proteins, induced sequence-specific decrease in the green or red fluorescence, respectively. These results suggest that O. dioica possesses a defence system against exogenous DNA and RNA, and that DNA fragment-induced gene silencing would be mediated through transcription blocking as well as mRNA degradation. This is the first report of DNAi in Metazoa.

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