scholarly journals In What Ways Do Synthetic Nucleotides and Natural Base Lesions Alter the Structural Stability of G-Quadruplex Nucleic Acids?

2017 ◽  
Vol 2017 ◽  
pp. 1-45 ◽  
Author(s):  
Janos Sagi
Keyword(s):  
Nucleic Acids ◽  
Building Blocks ◽  
Structural Studies ◽  
Nucleotide Analogs ◽  
Cellular Events ◽  
G Quadruplex ◽  
Natural Base ◽  
The Stability ◽  
Derivatives Of

Synthetic analogs of natural nucleotides have long been utilized for structural studies of canonical and noncanonical nucleic acids, including the extensively investigated polymorphic G-quadruplexes (GQs). Dependence on the sequence and nucleotide modifications of the folding landscape of GQs has been reviewed by several recent studies. Here, an overview is compiled on the thermodynamic stability of the modified GQ folds and on how the stereochemical preferences of more than 70 synthetic and natural derivatives of nucleotides substituting for natural ones determine the stability as well as the conformation. Groups of nucleotide analogs only stabilize or only destabilize the GQ, while the majority of analogs alter the GQ stability in both ways. This depends on the preferredsynorantiN-glycosidic linkage of the modified building blocks, the position of substitution, and the folding architecture of the native GQ. Natural base lesions and epigenetic modifications of GQs explored so far also stabilize or destabilize the GQ assemblies. Learning the effect of synthetic nucleotide analogs on the stability of GQs can assist in engineering a required stable GQ topology, and exploring thein vitroaction of the single and clustered natural base damage on GQ architectures may provide indications for the cellular events.

scholarly journals ALKOXYALKYL ESTERS OF NUCLEOTIDE ANALOGS INHIBIT POLYOMAVIRUS DNA REPLICATION AND LARGE T ANTIGEN ACTIVITIES

2020 ◽  
Author(s):  
Nichodemus O. Onwubiko ◽  
Suraya Diaz ◽  
Marcela Krecmerova ◽  
Heinz Peter Nasheuer
Keyword(s):  
Dna Replication ◽  
Tumor Antigens ◽  
Antiviral Agent ◽  
Dna Helicase ◽  
T Antigen ◽  
Nucleotide Analogs ◽  
Large Tumor ◽  
Nucleotide Analog ◽  
Derivatives Of

Polyomavirus-related infections are ubiqutious in immunocompromised individuals and in some cases are intractable and fatal. Due to lack of approved drugs to treat polyomavirus infections, cidofovir, a phosphonate nucleotide analog approved to treat cytomegalovirus infections has been repurposed as anti-polyomavirus agent. Cidofovir has been modified in various ways to improve its efficacies as broad-spectrum antiviral agent. However, the actual mechanisms and targets of cidofovir and its modified derivatives as anti-polyomavirus agents are still under research. Here, polyomavirus large tumor antigens (Tag) activities were identified as the viral target of cidofovir derivatives. The alkoxyalkyl-ester derivatives of cidofovir efficiently inhibit polyomavirus DNA replication in cell-free human extracts and a viral in vitro replication system only utilizing purified proteins. We present evidence that DNA helicase, and DNA binding activities of polyomavirus Tags are diminished in the presence of low concentrations of alkoxyalkyl-ester derivatives of cidofovir suggesting that the inhibition of viral DNA replication is at least in part mediated by inhibiting ssDNA and dsDNA binding activities of Tags. These findings show that the alkoxyalkyl-ester derivatives of cidofovir are effective in vitro without undergoing further conversions and conclude that the inhibitory mechanisms of nucleotide analog-based drugs are more complex than previously believed.

scholarly journals Overview of RNA G-quadruplex structures

2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Magdalena Małgowska
Keyword(s):  
Three Dimensional ◽  
Telomere Maintenance ◽  
Structural Studies ◽  
Biological Functions ◽  
Cellular Processes ◽  
Novel Drugs ◽  
G Quadruplex ◽  
Conformational Diversity

G-quadruplexes are non-canonical secondary structures which may be formed by guanine rich sequences, both in vitro and in living cells. The number of biological functions assigned to these structural motifs has grown rapidly since the discovery of their involvement in the telomere maintenance. Knowledge of the three-dimensional structures of G-quadruplexes plays an important role in understanding their conformational diversity, physiological functions, and in the design of novel drugs targeting G-quadruplexes. For the last decades, structural studies have been mainly focused on the DNA G-quadruplexes. Their RNA counterparts gained an increased interest along with still-emerging recognition of the central role of RNA in multiple cellular processes. In this review we focus on structural properties of RNA G-quadruplexes, based on high-resolution structures, available in RCSB PDB data base and on structural models. In addition, we point out to the current challenges in this field of research.

scholarly journals The binding of radioactive label from labelled phenacetin and related compounds to rat tissues in vivo and to nucleic acids and bovine plasma albumin in vitro

1971 ◽  
Vol 122 (3) ◽  
pp. 311-315 ◽  
Author(s):  
R. Nery
Keyword(s):  
Nucleic Acids ◽  
Rat Tissues ◽  
Biological Macromolecules ◽  
Plasma Albumin ◽  
Radioactive Label ◽  
Bovine Plasma ◽  
Derivatives Of ◽  
Related Compounds

1. acetyl-3H- and ethyl-14C-labelled derivatives of phenacetin and related compounds are described. 2. Radioactive label from the ethyl-14C-labelled derivatives of 4-nitrophenetole, 4-phenetidine and phenacetin binds in vitro to various extents to bovine plasma albumin, salmon sperm DNA and yeast RNA; the extent of binding is increased in the presence of a rat liver microsomal hydroxylating system and further increased when the microsomal enymes are induced by prior treatment of rats with 3-methylcholanthrene. 3. The ratios of the bound radioactive labels in vitro from [ethyl-14C]phenacetin, N-acetoxy[ethyl-14C]phenacetin, [acetyl-3H]phenacetin and [diacetyl-3H]N-acetoxyphenacetin per g-atom of DNA P, RNA P and per mol of protein in the absence of the microsomal system are approximately 1:60:11:863, 1:68:41:1835 and 1:88:713:2399 respectively. 4. Radioactive label from labelled phenacetin binds in vitro to all tissues examined, including the spleen, intestines, kidney and bladder; about 80% of the radioactivity bound to the liver is concentrated in the RNA and proteins. 5. Comparison of the relative extents of binding of radioactive label derived from equimolar amounts of labelled phenacetin, ethanol or acetate shows that the incorporation of labelled C2 units into tissues and biological macromolecules in vivo and in vitro may account for only a part of the total bound radioactive label derived from phenacetin and not at all from the incorporation of radioactive acetate into nucleic acids. 6. Some implications of these findings are discussed.

Synthesis and structure of fluoroindole nucleosides

2007 ◽  
Vol 85 (4) ◽  
pp. 283-292 ◽  
Author(s):  
Jelena Božilović ◽  
Jan W Bats ◽  
Joachim W Engels
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Driving Forces ◽  
Rna Stability ◽  
Building Blocks ◽  
Biologically Active ◽  
Dna And Rna ◽  
The Stability ◽  
Indole Synthesis

Chemically modified bases are frequently used to stabilize nucleic acids, to study the driving forces for nucleic acid structure formation, and to tune DNA and RNA hybridization conditions. Nucleoside analogues are chemical means to investigate hydrogen bonds, base stacking, and solvation as the three predominant forces that are responsible for the stability of nucleic acids. To obtain deeper insight into the contributions of these interactions to RNA stability, we decided to synthesize some novel nucleic acid analogues where the nucleobases are replaced by fluoroindoles. Fluorinated indoles can be compared with fluorinated benzimidazoles to determine the role of nitrogen in five-membered ring systems. The synthesis of fluoroindole ribonucleosides as well as the X-ray crystal structures of all synthesized fluoroindole ribonucleosides are reported here. These compounds could also be building blocks for a variety of biologically active RNA analogues.Key words: indoles, nucleosides, crystal structure, glycosilation, indole-synthesis.

Zum Wirkungsmechanismus von 1-Nitroso-3-nitro-1-methylguanidin (NNMG) bei der Mutationsauslösung / The Mode of Action of 1-Nitroso-3-nitro-1-methyl-guanidine (NNMG) in Mutagenesis

1969 ◽  
Vol 24 (7) ◽  
pp. 903-910 ◽  
Author(s):  
R. Süssmuth ◽  
F. Lingens
Keyword(s):  
Escherichia Coli ◽  
Citric Acid ◽  
Nucleic Acids ◽  
Mutation Rate ◽  
Control Experiment ◽  
Ph Dependence ◽  
The Stability ◽  
Escherichia Coli B

1. The stability of NNMG with respect to pH was investigated. A maximum, with a half-life of 40 hours, was found in phosphate-citric acid buffer at pH 5. The stability decreases quickly with increasing concentration of hydroxyl ions. At the optimal mutation rate (pH 6, 37°, and shaking) the half-live is only 14,4 hours.2. NNMG uptake (using labelled NNMG) and mutation rate in the range pH 3,5 — 8,0 show an optimum at pH 6,0/6,5 for both Escherichia coli B and the red ad- mutant E 188 of Saccharomyces cerevisiae. The pH-dependence of NNMG uptake and mutation rate is similar.3. The methylation of nucleic acids by means of [3H]-methyl-NNMG or [14C] -methyl-NNMG in phosphate-citric acid at 37° while shaking increases with the growing concentration of hydroxyl ions. At the optimal mutation rate, however, NNMG methylates relatively poor.4. Incorporation of radioactive NNMG into Escherichia coli B results in labelling of nucleic acids and proteins. The labelling of DNA shows an optimum at pH 6. The extent of methylation was found to be higher in vivo than in vitro.5. In the presence of cysteine or β-mercaptoethanol nucleic acids are methylated more intensively than in the cysteine-free control experiment. After one hour the methylation was about twentyfold higher in the presence of cysteine or β-mercaptoethanol compared to the cysteine-free control experiment. The methylation in presence of SH-compounds shows a maximum at pH 6. The explanation of both a higher methylation rate and its optimum at pH 6 suggests the activation of methylation by means of sulphhydryl-groups.

scholarly journals Depletion of Mammalian CCR4b Deadenylase Triggers Elevation of the p27Kip1 mRNA Level and Impairs Cell Growth

2007 ◽  
Vol 27 (13) ◽  
pp. 4980-4990 ◽  
Author(s):  
Masahiro Morita ◽  
Toru Suzuki ◽  
Takahisa Nakamura ◽  
Kazumasa Yokoyama ◽  
Takashi Miyasaka ◽  
...  
Keyword(s):  
Cell Growth ◽  
Mrna Level ◽  
3T3 Cells ◽  
Cellular Events ◽  
The Stability ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACT The stability of mRNA influences the abundance of cellular transcripts and proteins. Deadenylases play critical roles in mRNA turnover and thus are important for the regulation of various biological events. Here, we report the identification and characterization of CCR4b/CNOT6L, which is homologous to yeast CCR4 mRNA deadenylase. CCR4b is localized mainly in the cytoplasm and displays deadenylase activity both in vitro and in vivo. CCR4b forms a multisubunit complex similar to the yeast CCR4-NOT complex. Suppression of CCR4b by RNA interference results in growth retardation of NIH 3T3 cells accompanied by elevation of both p27 Kip1 mRNA and p27Kip1 protein. Reintroduction of wild-type CCR4b, but not mutant CCR4b lacking deadenylase activity, restores the growth of CCR4b-depleted NIH 3T3 cells. The data suggest that CCR4b regulates cell growth in a manner dependent on its deadenylase activity. We also show that p27 Kip1 mRNA is stabilized and its poly(A) tail is preserved in CCR4b-depleted cells. Our findings provide evidence that CCR4b deadenylase is a constituent of the mammalian CCR4-NOT complex and regulates the turnover rate of specific target mRNAs. Thus, CCR4b may be involved in various cellular events that include cell proliferation.

scholarly journals Study of stability of proline-containing derivatives of dopamine and serotonin in the biological media in vitro experiments

2019 ◽  
Vol 65 (6) ◽  
pp. 498-506 ◽  
Author(s):  
K.V. Shevchenko ◽  
L.A. Andreeva ◽  
I.Yu. Nagaev ◽  
V.P. Shevchenko ◽  
N.F. Myasoedov
Keyword(s):  
Leucine Aminopeptidase ◽  
Biologically Active ◽  
Carboxypeptidase Y ◽  
Vital Activity ◽  
Prolonged Action ◽  
Carboxypeptidase B ◽  
The Stability ◽  
First Time ◽  
Derivatives Of

Boc-Gly-Pro-DP, Z-Gly-Pro-DP, LA-Gly-Pro-DP, Boc-Gly-Pro-Srt, Z-Gly-Pro-Srt were synthesized for the first time. The stability of these compounds in the presence of leucine aminopeptidase, carboxypeptidase Y, carboxypeptidase B and proline endopeptidase (PEP) was determined. It turned out that the compounds are stable in the presence of aminopeptidases and carboxypeptidases. In the presence of PEP, dopamine (DP) and serotonin (Srt) are cleaved from the synthesized preparations. Thus, new proline-containing Srt and DP derivatives were obtained, Srt and DP could be gradually released from them. This suggest the possibility of a prolonged action of these biologically active compounds on the vital activity of cells and, consequently, of the whole organism.

Self-assembly of cellulose for creating green materials with tailor-made nanostructures

2021 ◽  
Author(s):  
Yuuki Hata ◽  
Takeshi Serizawa
Keyword(s):  
Nucleic Acids ◽  
Nanostructured Materials ◽  
Self Assembly ◽  
Building Blocks ◽  
Living Systems ◽  
Green Materials ◽  
Assembly Pathways

Inspired by living systems, biomolecules have been employed in vitro as building blocks for creating advanced nanostructured materials. In regard to nucleic acids, peptides, and lipids, their self-assembly pathways and...

scholarly journals Interaction of a Short Peptide with G-Quadruplex-Forming Sequences: An SRCD and CD Study

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1104
Author(s):  
Claudia Honisch ◽  
Eugenio Ragazzi ◽  
Rohanah Hussain ◽  
John Brazier ◽  
Giuliano Siligardi ◽  
...  
Keyword(s):  
Circular Dichroism ◽  
Dna Sequences ◽  
Parallel Structure ◽  
Dna And Rna ◽  
Cellular Events ◽  
G Quadruplex ◽  
The Stability ◽  
Circular Dichroïsm ◽  
Sodium And Potassium ◽  
Temperature Melting

G-quadruplex (G4) forming DNA sequences were recently found to play a crucial role in the regulation of genomic processes such as replication, transcription and translation, also related to serious diseases. Therefore, systems capable of controlling DNA and RNA G-quadruplex structures would be useful for the modulation of various cellular events. In particular, peptides represent good candidates for targeting G-quadruplex structures, since they are easily tailored to enhance their functionality. In this work, we analyzed, by circular dichroism and synchrotron radiation circular dichroism spectroscopies, the interaction of a 25-residue peptide deriving from RHAU helicases (Rhau25) with three G-quadruplex-forming oligonucleotide sequences, in both sodium- and potassium-containing buffers, the most relevant monovalent cations in physiological conditions. The peptide displayed greater affinity for the G4 sequences adopting a parallel structure. However, it showed the ability to also interact with antiparallel or hybrid G-quadruplex structures, inducing a conformation conversion to the parallel structure. The stability of the oligonucleotide structure alone or in presence of the Rhau25 peptide was studied by temperature melting and UV denaturation experiments, and the data showed that the interaction with the peptide stabilized the conformation of oligonucleotide sequences when subjected to stress conditions.

Formation and Structure of Casein Micelles in Lactating Mammary Tissue

1970 ◽  
Vol 28 ◽  
pp. 150-151
Author(s):  
Robert J. Carroll ◽  
Marvin P. Thompson ◽  
Harold M. Farrell
Keyword(s):  
Size Distribution ◽  
G Protein ◽  
Milk Proteins ◽  
Mammary Tissue ◽  
Colloidal System ◽  
Casein Micelles ◽  
The Stability

Milk is an unusually stable colloidal system; the stability of this system is due primarily to the formation of micelles by the major milk proteins, the caseins. Numerous models for the structure of casein micelles have been proposed; these models have been formulated on the basis of in vitro studies. Synthetic casein micelles (i.e., those formed by mixing the purified αsl- and k-caseins with Ca2+ in appropriate ratios) are dissimilar to those from freshly-drawn milks in (i) size distribution, (ii) ratio of Ca/P, and (iii) solvation (g. water/g. protein). Evidently, in vivo organization of the caseins into the micellar form occurs in-a manner which is not identical to the in vitro mode of formation.

Sign in / Sign up

Export Citation Format

Share Document