Practical and reliable synthesis of 2',3',5',5 ″-tetradeuterated uridine derivatives.
Practical and reliable synthesis of 2',3',5',5″-tetradeuterated uridine derivatives. Nucleosides Nucleotides Nucleic Acids. 2019 Oct 24;:1-9 Authors: Miyamoto N, Ohno H, Kitamura Y, Park K, Sawama Y, Sajiki H, Kitade Y Abstract Deuterated drugs are valuable in the fields of drug discovery and medicinal chemistry. 2',3',5',5″-tetradeuterated uridine derivatives were synthesised from 2,3,5,5'-selectively tetradeuterated ribose using Sajiki's H-D exchanged Ru/C-H2-D2O-NaOH system and silyl-Hilbert-Johnson methods. The total deuterium content of the tetradeuterated uridines was over 92% using e...
Source: Nucleosides, Nucleotides and Nucleic Acids - October 26, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Limits of using oligonucleotides for allele-selective inhibition at trinucleotide repeat sequences - targeting the CAG repeat within ataxin-1.
Authors: Hu J, Corey DR Abstract Trinucleotide repeats are responsible for many genetic diseases. Previous studies have shown that duplex RNAs (dsRNAs) can be used to target expression of a mutant repeat allele while leaving expression of the wild-type allele untouched, creating opportunities for allele-selective inhibition and better therapeutic outcomes. In contrast to successes with other genes, we report here that we cannot achieve allele-selective inhibition when targeting the expanded CAG repeat within Ataxin-1 (ATXN1), the cause of spinal cerebellar ataxia-1 (SCA1). The most likely explanation for this unfav...
Source: Nucleosides, Nucleotides and Nucleic Acids - October 26, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Selective cross-linking behavior of oligodeoxyribonucleotides containing 2'-O-[N-(4,5',8-trimethylpsoralen-4'-ylmethylcarbamoyl)]adenosine to mutant H-ras DNA.
Authors: Yamayoshi A, Higuchi M, Sakai Y, Kobori A, Yamamoto T, Shibata T, Murakami A Abstract Point mutations are well characterized activators of oncogenes but are often indistinguishable using common gene technologies. In general, the precise sites of point-mutated oncogenes are difficult to distinguish under physiological conditions primarily because single nucleotide mismatch do not affect the annealing temperatures of DNA probes sufficiently. To address this limitation, we developed photo-responsive oligodeoxyribonucleotides containing 2'-O-[N-(4,5',8-trimethylpsoralen-4'-ylmethylcarbamoyl)]adenosine (Ps-amd-...
Source: Nucleosides, Nucleotides and Nucleic Acids - October 26, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Cooperative recognition of a repetitive sequence through consecutive formation of triplex and duplex structures.
Authors: Kitamura Y, Nagai K, Furuzono T, Katsuda Y, Ihara T Abstract Cooperative recognition of a repetitive sequence was performed with a short single DNA strand consisting of duplex- and triplex-forming regions modified with a ligand (benzoquinoquinoxaline) to stabilize a triplex structure. The former region was complementary with one unit of a repetitive sequence and the latter had a sequence that can bind with a cognate duplex formed by another DNA molecule bound on an adjacent site. The DNA binding to one unit of the repetitive sequence is expected to facilitate the second binding to an adjacent unit through ...
Source: Nucleosides, Nucleotides and Nucleic Acids - October 24, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Effect of modular conjugation strategy for N-acetylgalactosamine-targeted antisense oligonucleotides.
Authors: Yamamoto T, Sawamura M, Terada C, Kashiwada K, Wada F, Yamayoshi A, Obika S, Harada-Shiba M Abstract The asialoglycoprotein receptor (ASGPr) and N-acetylgalactosamine (GalNAc) is one of the most reliable receptor-ligand combinations for delivering antisense oligonucleotides (ASOs) to the liver. Here, we show that a modular GalNAc conjugation strategy allows us to reinforce the activity of the parent, naked 2',4'-BNA/LNA gapmer targeting apolipoprotein B. The conjugation partly reduced a possible hepatotoxicity of the parent ASO. The structure-activity study revealed the significance of the metabolic suscep...
Source: Nucleosides, Nucleotides and Nucleic Acids - October 17, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Tips for improving the quality and quantity of the extracted DNA from exhaled breath condensate samples.
Authors: Kazeminasab S, Emamalizadeh B, Jouyban-Gharamaleki V, Taghizadieh A, Khoubnasabjafari M, Jouyban A Abstract There is a growing interest in the tracking of genetic and epigenetic alterations in exhaled breath condensate (EBC) samples. The effects of different procedures on the quality and quantity of DNA in EBC were studied. The results demonstrated that sodium acetate precipitation and oligo (dT) improved the quality of the extracted DNA significantly (p 
Source: Nucleosides, Nucleotides and Nucleic Acids - October 16, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Synthesis of selenomethylene-locked nucleic acids (SeLNA) nucleoside unit bearing an adenine base.
In this study, we found the heat-labile property of SeLNA-A. It is necessary to know more precise characteristics of SeLNA to achieve its oligonucleotides synthesis. PMID: 31608780 [PubMed - as supplied by publisher] (Source: Nucleosides, Nucleotides and Nucleic Acids)
Source: Nucleosides, Nucleotides and Nucleic Acids - October 16, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Cationic copolymer-chaperoned short-armed 10-23 DNAzymes.
In this study, we evaluated activities of DNAzymes with substrate-binding arms (S-arms) of various lengths. The copolymer promoted DNAzyme reactivity and turnover efficacy, and, depending on S-arm length, maximally accelerated the reaction rate by 250-fold compared to the rate in the absence of copolymer. The copolymer permitted up to six nucleotides truncation of the S-arms having initial length of 10 and 11 nucleotides without loss of catalytic efficiency, enable tuning of the optimal temperature ranging from 30 to 55 °C. The approach might be useful for the development of DNAzyme systems targeting short or hi...
Source: Nucleosides, Nucleotides and Nucleic Acids - October 16, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Repair of trapped topoisomerase II covalent cleavage complexes: Novel proteasome-independent mechanisms.
In this study, we analyze the repair of etoposide-induced TOP2ccs in wild-type and TDP2-deficient (TDP2-/-) TK6 cells in the absence and presence of MG132, a potent proteasome inhibitor. The results suggested that TOP2ccs were repaired by proteasome-dependent and proteasome-independent pathways. Both proteasome-dependent and proteasome-independent pathways were further subdivided into TDP2-dependent and TDP2-independent pathways, indicating that four pathways operate in the repair of TOP2ccs. In cell survival assays, MG132 increased the etoposide sensitivity of TDP2-/- cells, supporting the TDP2-independent and proteasome-...
Source: Nucleosides, Nucleotides and Nucleic Acids - October 16, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

A nanocarrier for the mitochondrial delivery of nucleic acids to cardiomyocytes.
In this study, H9c2 cells a type of rat cardiac myoblasts, were used as model cardiac muscle cells. The use of a lipid composition used to prepare the β-MEND (where MEND denotes multifunctional envelope-type nano device) permitted the particles to be efficiently internalized by H9c2 cells, as evidenced by flow cytometry analyses. Intracellular observations by confocal laser scanning microscopy showed that the β-MEND efficiently accumulated in mitochondria of H9c2 cells. We also constructed an RP/β-MEND that contained a mitochondrial RNA aptamer to achieve mitochondrial delivery in H9c2 cells. The successful ...
Source: Nucleosides, Nucleotides and Nucleic Acids - October 11, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Intracellular metabolism and potential cardiotoxicity of a β-D-2'-C-methyl-2,6-diaminopurine ribonucleoside phosphoramidate that inhibits hepatitis C virus replication.
Intracellular metabolism and potential cardiotoxicity of a β-D-2'-C-methyl-2,6-diaminopurine ribonucleoside phosphoramidate that inhibits hepatitis C virus replication. Nucleosides Nucleotides Nucleic Acids. 2019 Oct 09;:1-21 Authors: Tao S, Zhou L, Zhang H, Zhou S, Amiralaei S, Shelton J, Ehteshami M, Jiang Y, Amblard F, Coats SJ, Schinazi RF Abstract β-D-2'-C-Methyl-2,6-diaminopurine ribonucleoside (2'-C-Me-DAPN) phosphoramidate prodrug (DAPN-PD) is a selective hepatitis C virus inhibitor that is metabolized intracellularly into two active metabolites: 2'-C-Methyl-DAPN triphosphate (2'-C-Me...
Source: Nucleosides, Nucleotides and Nucleic Acids - October 11, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Synthesis and anti-H5N1 virus activity of triazole- and oxadiazole-pyrimidine hybrids and their nucleoside analogs.
Authors: Tolan HEM, El-Sayed WA, Tawfek N, Abdel-Megeid FME, Kutkat OM Abstract New 1,2,3-triazole glycosides and 1,2,4-thioglycosides incorporating a substituted pyrimidinedione ring system were synthesized via click dipolar cycloaddition and heterocyclization of hydrazine-1-carbodithioate derivatives, respectively. The sugar hydrazine derivatives linked aminodimethyluracil were also prepared. In addition, the oxadiazoline substituted with acyclic sugar moieties linked to the pyrimidinedione as acyclic nucleoside analogs were synthesized. The antiviral activity of the synthesized compounds against avian influenza ...
Source: Nucleosides, Nucleotides and Nucleic Acids - October 11, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

A convenient route to synthesize N2-(isobutyryl)-9-(carboxymethyl)guanine for aeg-PNA backbone.
Authors: Datta D Abstract Synthesis of exclusive N2-(isobutyryl)-9-(carboxymethyl)guanine, an important moiety for peptide nucleic acid synthesis has been reported through a high-yielding reaction scheme starting from 6-chloro-2-amino purine. Crystal structures of two intermediates confirmed the formation of N9-regioisomer. This new synthetic route can potentially replace the conventional tedious method with moderate overall yield. PMID: 31588835 [PubMed - as supplied by publisher] (Source: Nucleosides, Nucleotides and Nucleic Acids)
Source: Nucleosides, Nucleotides and Nucleic Acids - October 9, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Synthesis of 7-trifluoromethyl-7-deazapurine ribonucleoside analogs and their monophosphate prodrugs.
Authors: Cho JH, Bassit LC, Amblard F, Schinazi RF Abstract Novel 7-trifluoromethyl-7-deazapurine ribonucleoside analogs (13a-c) and their Protides (15a-c) were successfully synthesized from ribolactol or 1-α-bromo-ribose derivatives using Silyl-Hilbert-Johnson or nucleobase-anion substitution reactions followed by key aromatic trifluoromethyl substitution. Newly prepared compounds were evaluated against a panel of RNA viruses, including HCV, Ebola or Zika viruses. PMID: 31588837 [PubMed - as supplied by publisher] (Source: Nucleosides, Nucleotides and Nucleic Acids)
Source: Nucleosides, Nucleotides and Nucleic Acids - October 9, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Inhibition of breast cancer cell proliferation with anti-microRNA oligonucleotides flanked by interstrand cross-linked duplexes.
This study investigated the effects of anti-microRNA-21 (miR-21) AMO modified with CLDs on breast cancer cells without using reporter assay. The CLD-modified AMO suppressed breast cancer cell proliferation for a long duration compared to other types of AMOs. In addition, it expectedly up-regulated the miR-21-controlled expression of tumor suppressor genes. Therefore, an AMO flanked by CLDs can be a promising strategy for breast cancer treatment. PMID: 31583946 [PubMed - as supplied by publisher] (Source: Nucleosides, Nucleotides and Nucleic Acids)
Source: Nucleosides, Nucleotides and Nucleic Acids - October 6, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Zirconia-Cu(I) stabilized copper oxide mesoporous nano-catalyst: Synthesis and DNA reactivity of 1,2,4-oxadiazole-quinolinepeptidomimetics-based metal(II) complexes.
Authors: Aravinda T, Vinay Kumar B, Raghu MS, Parusharam L, Rao S Abstract Contemporary research reveals an undemanding protocol for the catalytic synthesis of 1,2,4-oxadiazole-quinolinepeptide in the incidence of a cost-effective and reusable mesoporous ZrO2-supported Cu2O (Cu2ZrO3) catalyst. This paper depicts a unique system for peptide bond synthesis staying away from toxic solvents and reactants. The catalyst was reused for four cycles without noteworthy loss in the activity, and the catalyst was genuinely heterogeneous. The method followed a simple workup procedure, and no column chromatography was needed. Fu...
Source: Nucleosides, Nucleotides and Nucleic Acids - October 4, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Structure-activity relationship of pseudoknot-type hammerhead ribozyme reveals key structural elements for enhanced catalytic activity †.
Structure-activity relationship of pseudoknot-type hammerhead ribozyme reveals key structural elements for enhanced catalytic activity†. Nucleosides Nucleotides Nucleic Acids. 2019 Oct 03;:1-13 Authors: Yamada M, Tanaka Y Abstract The pseudoknot-type hammerhead ribozyme (PK-HHRz) is known to be activated by a pseudoknot interaction between loops I and II. To obtain maximal activation through the pseudoknot formation, we studied the structure-activity relationship of PK-HHRz. From these studies, the structural requirements of the PK-HHRz cleavage reaction were clearly defined. In addition, we dis...
Source: Nucleosides, Nucleotides and Nucleic Acids - October 4, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Synthesis and biological evaluation of a MraY selective analogue of tunicamycins.
Authors: Yamamoto K, Sato T, Hikiji Y, Katsuyama A, Matsumaru T, Yakushiji F, Yokota SI, Ichikawa S Abstract Tunicamycins, which are nucleoside natural products, inhibit both bacterial phospho-N-acetylmuraminic acid (MurNAc)-pentapeptide translocase (MraY) and human UDP-N-acetylglucosamine (GlcNAc): polyprenol phosphate translocase (GPT). The improved synthesis and detailed biological evaluation of an MraY-selective inhibitor, 2, where the GlcNAc moiety was modified to a MurNAc amide, has been described. PMID: 31566068 [PubMed - as supplied by publisher] (Source: Nucleosides, Nucleotides and Nucleic Acids)
Source: Nucleosides, Nucleotides and Nucleic Acids - October 1, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Translational control by secondary-structure formation in mRNA in a eukaryotic system.
Authors: Kawaguchi D, Shimizu S, Abe N, Hashiya F, Tomoike F, Kimura Y, Abe H Abstract Eukaryotic mRNA has a cap structure at the 5' end and a poly(A) tail at the 3' end. The cap and poly(A) tail form a complex with multiple translation factors, and mRNA forms a circularized structure called a closed-loop model. This circularized structure reportedly not only stabilizes mRNA but also promotes ribosome recycling during translation, which improves translation efficiency. We designed an artificial mRNA that forms a circularized structure without a cap structure and poly(A) tail and found that its translational efficie...
Source: Nucleosides, Nucleotides and Nucleic Acids - October 1, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

DNA groove-binding and acid-base properties of a Ru(II) complex containing anthryl moieties.
Authors: Yin HJ, Zhang AG, Gao LH, Zhao H, Wang KZ Abstract DNA groove binders have been poorly studied as compared to the intercalators. A novel Ru(II) complex of [Ru(aeip)2(Haip)](PF6)2 {Haip = 2-(9-anthryl)-1H-imidazo[4,5-f][1,10]phenanthroline and aeip = 2-(anthracen-9-yl)-1-ethyl-imidazo[4,5-f][1, 10]phenanthroline} is synthesized and characterized by elemental analysis, 1H NMR spectroscopy and mass spectrometry. The complex is evidenced to be a calf-thymus DNA groove binder with a large intrinsic binding constant of 106 M-1 order of magnitude as supported by UV-visible absorption spectral t...
Source: Nucleosides, Nucleotides and Nucleic Acids - October 1, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Nucleoside analogs as a radiosensitizer modulating DNA repair, cell cycle checkpoints, and apoptosis.
Authors: Yasui H, Iizuka D, Hiraoka W, Kuwabara M, Matsuda A, Inanami O Abstract The combination of low dose of radiation and an anticancer drug is a potent strategy for cancer therapy. Nucleoside analogs are known to have a radiosensitizing effects via the inhibition of DNA damage repair after irradiation. Certain types of nucleoside analogs have the inhibitory effects on RNA synthesis, but not DNA synthesis, with multiple functions in cell cycle modulation and apoptosis. In this review, the most up-to-date findings regarding radiosensitizing nucleoside analogs will be discussed, focusing especially on the mechani...
Source: Nucleosides, Nucleotides and Nucleic Acids - September 29, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Design, synthesis and antiviral evaluation of novel acyclic phosphonate nucleotide analogs with triazolo[4,5-b]pyridine, imidazo[4,5-b]pyridine and imidazo[4,5-b]pyridin-2(3H)-one systems.
Authors: Hartwich A, Zdzienicka N, Schols D, Andrei G, Snoeck R, Głowacka IE Abstract A new series of phosphonylated triazolo[4,5-b]pyridine (1-deaza-8-azapurine), imidazo[4,5-b]pyridine (1-deazapurine) and imidazo[4,5-b]pyridin-2(3H)-one (1-deazapurin-8-one) were synthesized from 2-chloro-3-nitropyridine and selected diethyl ɷ-aminoalkylphosphonates followed by reduction of the nitro group and cyclization. In the final step O,O-diethylphosphonates were transformed into the corresponding phosphonic acids. All synthesized compounds were evaluated in vitro for inhibitory activity against a broad variety of DNA and ...
Source: Nucleosides, Nucleotides and Nucleic Acids - September 27, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Development of gapmer antisense oligonucleotide with deoxyribonucleic guanidine (DNG) modifications.
Authors: Kojima N, Shrestha AR, Akisawa T, Piao H, Kizawa H, Ohmiya Y, Kurita R Abstract The properties of gapmer antisense oligonucleotide (ASO) flanked by deoxyribonucleic guanidine (DNG) were investigated for the potential application in antisense technology. DNG is a unique nucleotide analog which has a positively charged internucleotide guanidinium linkage instead of negatively charged phosphodiester backbone linkage. We prepared a gapmer ASO containing DNG units at both wings of the sequence and compared its properties with 2',4'-BNA/LNA gapmer ASOs with phosphorothioate (PS) backbone. Although DNG gapmer sho...
Source: Nucleosides, Nucleotides and Nucleic Acids - September 27, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Synthesis and characterization of 4'-C-guanidinomethyl-2'-O-methyl-modified RNA oligomers.
This study investigated the synthesis and properties of 4'-C-guanidinomethyl-2'-O-methyluridine and RNAs containing the analog. Thermal and thermodynamic stabilities of double-stranded RNAs (dsRNAs) containing the nucleoside analog were examined. It was found that although the analog decreased the thermal and thermodynamic stabilities of dsRNA, it had base-discrimination ability. The 4'-C-guanidinomethyl modification increased stability of RNAs in a buffer containing serum. Furthermore, small interference RNAs incorporating one analog at the passenger strand still preserved their RNA interference activities. It was suggest...
Source: Nucleosides, Nucleotides and Nucleic Acids - September 20, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

A highly constrained nucleic acid analog based on α-l-threosamine.
A highly constrained nucleic acid analog based on α-l-threosamine. Nucleosides Nucleotides Nucleic Acids. 2019 Sep 17;:1-10 Authors: Morihiro K, Okamoto A Abstract Chemically modified oligonucleotides (ONs) have recently gained much attention as therapeutic materials because of their improved properties. Here, a newly designed nucleic acid analog based on α-l-threosamine (named cTNA) is reported. cTNA has a "dual" constrained structure, with a bridged sugar moiety and shorter phosphoramidate backbone, to reduce the entropy loss during the hybridization. Unexpectedly, ONs containin...
Source: Nucleosides, Nucleotides and Nucleic Acids - September 20, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Synthesis and evaluation of the anti-hepatitis B virus activity of 4'-Azido-thymidine analogs and 4'-Azido-2'-deoxy-5-methylcytidine analogs: structural insights for the development of a novel anti-HBV agent.
Authors: Onitsuka K, Tokuda R, Kuwata-Higashi N, Kumamoto H, Aoki M, Amano M, Kohgo S, Das D, Haraguchi K, Mitsuya H, Imoto S Abstract Hepatitis B virus (HBV) infection is a major worldwide health problem that requires the development of improved antiviral therapies. Here, a series of 4'-Azido-thymidine/4'-Azido-2'-deoxy-5-methylcytidine derivatives (6, 10-15) were synthesized, and their anti-HBV activities evaluated. Compounds 10-15 were synthesized via an SNAr reaction of 18, in which the 4-position of the thymine moiety was activated as the 2,4,6-triisopropylbenzenesulfonate. Compounds 11-15 showed no antiviral ...
Source: Nucleosides, Nucleotides and Nucleic Acids - September 14, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Effects of metal ions on thermal stabilities of DNA duplexes containing homo- and heterochiral mismatched base pairs: comparison of internal and terminal substitutions.
Authors: Funai T, Adachi N, Aotani M, Wada SI, Urata H Abstract The effects of metal ions on the stabilities of duplexes containing a D-homochiral and heterochiral mismatched base pairs were studied. In some duplexes containing an internal mismatched base pair, significant stabilization by HgII and AgI ions was observed. While, in duplexes containing a terminal mismatched base pair, only the duplexes containing T-T and LT-T mispairs were significantly stabilized by HgII ions, and the stabilities of the duplexes containing T-T and LT-T mispairs exceeded those of the corresponding homochiral matched duplex. The resul...
Source: Nucleosides, Nucleotides and Nucleic Acids - September 14, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Design of 2'-O-methyl RNA and DNA double-stranded oligonucleotides: naturally-occurring nucleotide components with strong RNA interference gene expression inhibitory activity.
In this study, asymmetrical 18 base-paired double-strand oligonucleotides comprised of alternately combined DNAs and 2'-O-methyl RNAs, denoted as MED-siRNA, were evaluated. These modified oligonucleotides showed high RNase resistance, a reduced immune response, a highly efficient cleavage of target mRNA with binding to Argonaute 2 (Ago2) via RNA interference, and the subsequent reduction of target protein expression. These findings suggest the possibility of alternatives to unmodified siRNAs with potential use in therapeutics. PMID: 31509065 [PubMed - as supplied by publisher] (Source: Nucleosides, Nucleotides and Nucleic Acids)
Source: Nucleosides, Nucleotides and Nucleic Acids - September 13, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Effect of phytic acid on postprandial serum uric acid level in healthy volunteers: a randomized, double-blind, crossover study.
This study investigated the effect of phytic acid on postprandial serum uric acid (SUA) in humans. This randomized, double-blind, crossover design study included 48 healthy subjects with normal fasting SUA. Subjects consumed a control drink and a phytic acid drink with purine-rich food, and serum and urine uric acid levels were measured for 360 min after purine loading. Phytic acid lowered the incremental area under the curve (0-360 min) and incremental maximum concentration of SUA after purine loading (p 
Source: Nucleosides, Nucleotides and Nucleic Acids - August 31, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Survey of ribose ring pucker of signaling nucleosides and nucleotides.
Authors: Salmaso V, Jacobson KA Abstract The ribose of protein-bound nucleosides and nucleotides displays preferred conformations (usually either North or South), which can be exploited to design enhanced analogs having chemically fixed conformations. We introduce a computational protocol for assembling data from the protein database (PDB) on the ribose and ribose-like conformation of small molecule ligands when complexed with purinergic signaling proteins (including receptors, enzymes and transporters, and related intracellular pathways). Some targets prefer exclusively North (adenosine and P2Y1 receptors, CD73, a...
Source: Nucleosides, Nucleotides and Nucleic Acids - August 30, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Synthesis of D-like and L-like 5'-fluoro-5'-deoxy-1',6'-isoneplanocins and their antiviral activity including Ebola.
Authors: Liu C, Chen Q, Schneller S Abstract In exploring the 1',6'-isoneplanocin structural framework for antiviral compound development, both the D-like and L-like 5'-fluoro-5'-deoxy analogs have been synthesized from readily available cyclopentenyl iodides and adenine in five steps. Antiviral evaluation found D-like 5'-fluoro-5'-deoxy-1',6'-isoneplanocin to display less broad-spectrum antiviral effects than the parent D-like including weaker activity against Ebola and norovirus. The L-like enantiomer was devoid of any activity, contrary to the parent L-like compound. PMID: 31448686 [PubMed - as supplied by p...
Source: Nucleosides, Nucleotides and Nucleic Acids - August 28, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

An alternative method for the synthesis of 2'-halogeno-1',2'-unsaturated uridine derivatives through syn-elimination of pivalic acid of 2'-halogeno- 2'-deoxy-1'-pivaloyloxyuracil nucleoside: preparation of its 2'-C-branched nucleosides.
Authors: Haraguchi K, Gen E, Kumamoto H, Itoh Y, Tanaka H Abstract An alternative method for the preparation of 2'-bromo- (5b) and 2'-iodo- (5c) 1',2'-unsaturated uracil nucleosides has been developed. The protocol was on the basis of the syn-elimination of pivalic acid from 2'-bromo-(7a,b) and 2'-iodo-(9a,b) 1'-pivaloyloxy-2'-deoxyuridine derivatives, which were derived from the halo-pivaloyloxylation of 3',5'-bis-O-TBDMS-1',2'-unsaturated uridine 1. Compounds 5b and 5c were shown to serve as versatile synthons for the respective 2'-C-branched 1',2'-unsaturated uracil nucleosides, through palladium-catalyzed cross...
Source: Nucleosides, Nucleotides and Nucleic Acids - August 21, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Bacterial classification with convolutional neural networks based on different data reduction layers.
Authors: Abd-Alhalem SM, Soliman NF, Eldin S, Abd Elrahman SE, Ismail NA, El-Rabaie EM, El-Samie FEA Abstract For high accuracy classification of DNA sequences through Convolutional Neural Networks (CNNs), it is essential to use an efficient sequence representation that can accelerate similarity comparison between DNA sequences. In addition, CNN networks can be improved by avoiding the dimensionality problem associated with multi-layer CNN features. This paper presents a new approach for classification of bacterial DNA sequences based on a custom layer. A CNN is used with Frequency Chaos Game Representation (FCGR) ...
Source: Nucleosides, Nucleotides and Nucleic Acids - August 18, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Design And Synthesis Of An Azabicyclic Nucleoside Phosphoramidite For Oligonucleotide Antisense Constructs.
We report the synthesis and biophysical evaluation of an azabicycle dinucleotide with restricted γ, β, and ε torsion angles, featuring the introduction of a piperidine ring that locks the conformation of the nucleoside into an RNA-type nucleic acid. The conceptual basis of the design is predicated upon the notion that the conformation of the phosphate group linking two RNA nucleotides can be approximated with an azabicyclic phosphoramidite which may also benefit from a unique stereoelectronic effect. PMID: 31380707 [PubMed - as supplied by publisher] (Source: Nucleosides, Nucleotides and Nucleic Acids)
Source: Nucleosides, Nucleotides and Nucleic Acids - August 7, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Nucleoside dimers analogs containing floxuridine and thymidine with unnatural linker groups: synthesis and cancer line studies. Part III.
Authors: Baraniak D, Ruszkowski P, Baranowski D, Framski G, Boryski J Abstract Two series of novel fluorinated nucleosides dimers with an unnatural 1,2,3-triazole linkage were synthesized. The obtained molecules were prepared using "click" chemistry approach based on copper(I) catalyzed Huisgen azide-alkyne cycloaddition. It was performed between 3'- and 5'-azido-nucleosides as the azide components, and the 3'-O- and 5'-O-propargyl-nucleosides as the alkyne components. Based on analysis of the 3 JHH, 3 JH1'C2 and 3 JH1'C6 we estimated conformational preferences of sugar part and orientation around glycosi...
Source: Nucleosides, Nucleotides and Nucleic Acids - August 7, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Synthesis of 2'-aminouridine derivatives as an organocatalyst for Diels-Alder reaction †.
Synthesis of 2'-aminouridine derivatives as an organocatalyst for Diels-Alder reaction †. Nucleosides Nucleotides Nucleic Acids. 2019 Jul 30;:1-19 Authors: Wakamatsu H, Itoh M, Natori Y, Yoshimura Y Abstract To develop a novel asymmetric organocatalyst based on a ribonucleoside skeleton, we designed and synthesized 2'-aminouridine derivatives. The synthesized 2'-aminouridines having bulky substituents at both base and sugar moieties could catalyze the Diels-Alder reaction between cinnamaldehyde and cyclopentadiene. However, the optical purities of the resulting products were unexpectedly low. ...
Source: Nucleosides, Nucleotides and Nucleic Acids - August 1, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

No enhancing effects of plasmid-specific histone acetyltransferase recruitment system on transgene expression in vivo.
In this study, the same approach was applied for transgene expression in mice. The activator and reporter plasmid DNAs bearing the genes for GAL4-HAT and Gaussia princeps luciferase, respectively, were co-administered into the mouse liver by hydrodynamics-based tail vein injection, and the Gaussia luciferase activity in serum was measured for two weeks. Unexpectedly, the co-injection of the GAL4-HAT and luciferase plasmid DNAs seemed to decrease, rather than increase, luciferase expression. Moreover, the co-injection apparently reduced the amount of luciferase DNA in the liver. These results indicated that this system is i...
Source: Nucleosides, Nucleotides and Nucleic Acids - July 15, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

N6-methyl adenosine in siRNA evades immune response without reducing RNAi activity.
Authors: Imaeda A, Tomoike F, Hayakawa M, Nakamoto K, Kimura Y, Abe N, Abe H Abstract siRNA is a powerful method to suppress specific gene expression and has recently been utilized for molecular biology as well as medicine. However, introduction of dsRNA stimulates immune-responses as side-effects. In the present study, we utilized N6-methyl adenosine, one of the natural modified nucleosides, instead of adenosine in siRNA. When adenosine in the passenger or guide strand of siRNA was completely replaced with N6-methyl adenosine, the immune response against siRNA was evaded without any reduction in RNAi activity. Thi...
Source: Nucleosides, Nucleotides and Nucleic Acids - July 14, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

DNA interaction studies of rhenium compounds with Schiff base chelates encompassing biologically relevant moieties.
Authors: Ismail MB, Booysen IN, Akerman MP Abstract Herein, we report the DNA interaction studies of rhenium(I) and -(V) compounds with Schiff base chelates encompassing biologically relevant moieties. More specifically, the DNA interaction capabilities of these rhenium complexes were probed using Gel Electrophoresis and Calf Thymus-DNA titrations monitored by temperature-controlled electronic spectroscopy. The DNA binding modes of the metal compounds were corroborated by molecular docking simulations. In addition, the synthesis and characterization of a novel facial tricarbonyl rhenium(I) compound, fac-[Re(chrs)(C...
Source: Nucleosides, Nucleotides and Nucleic Acids - July 12, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Synthesis of 1,1,2-trisubstituted cyclopropane nucleosides in enantiomerically pure forms.
Authors: Fushihara D, Fukuda H, Abe H, Shuto S Abstract Due to the unique rigid and small steric feature of cyclopropane, cyclopropane nucleosides (CPNs) in which the ribose (deoxyribose) of nucleosides are replaced by a hydroxy-substituted cyclopropane, are of great biological interest. Novel 1,1,2-trisubstituted cyclopropane nucleosides were synthesized in enantiomerically pure forms as potential antiviral agents. In the synthesis, two cyclopropane tosylates, which were prepared from chiral cyclopropane lactones previously reported by us, were used effectively as common intermediates for the CPNs. These CPNs are ...
Source: Nucleosides, Nucleotides and Nucleic Acids - June 14, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Nucleoside dimers analogues with a 1,2,3-triazole linkage: conjugation of floxuridine and thymidine provides novel tools for cancer treatment. Part II.
We report on the synthesis and properties of two groups of nucleoside dimers analogs possessing a different arrangement of the 1,4-disubstituted 1,2,3-triazole linkage. Based on analysis of the 3JHH, 3JH1'C2, and 3JH1'C6 we estimated conformational preferences of sugar part and orientation around glycosidic bond. These compounds show moderate anticancer activity, with cytostatic studies in three different cancer cell lines. PMID: 31177919 [PubMed - as supplied by publisher] (Source: Nucleosides, Nucleotides and Nucleic Acids)
Source: Nucleosides, Nucleotides and Nucleic Acids - June 12, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Intercalation of manganese-mefenamic acid complex into double stranded of calf thymus DNA.
Authors: Shahabadi N, Jamshidi Z, Hadidi S, Shiri F, Fatahi N Abstract The interaction of the [Mn(mef)2(phen)H2O] complex in which mef is mefenamic acid drug and phen is 1,10 phenanthrolin ligand with calf thymus DNA (ct-DNA) was studied by using different spectroscopic methods, molecular docking and viscometery. The competitive fluorescence and UV-Vis absorption spectroscopy indicated that the complex interacted with ctDNA via intercalating binding mode with the binding constant of 1.16 × 104 Lmol-1. The thermodynamic studies showed that the reaction between the complex and ctDNA is exothermic....
Source: Nucleosides, Nucleotides and Nucleic Acids - June 9, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Design, synthesis, in vitro anticancer, antioxidant and antibacterial activity; DNA/BSA binding, photoleavage and docking studies of Cu(II) ternary metal complexes.
Authors: Mudavath R, Vuradi RK, Bathini U, Narsimha N, Kunche S, Sunitha S, Ch SD Abstract Three mononuclear, mixed ligand ternary Cu(II) complexes of 3-((Z)-1-(2-hydroxyphenylimino)ethyl)-4-hydroxy-6-methyl-2H-pyran-2-one (HEHMP) viz; [Cu-(Phen) (HEHMP)] (1a), [Cu-(Bpy)(HEHMP)] (1 b) and [Cu-Bpy(NCS)(HEHMP)] (1c) were synthesized and characterized by data obtained from various spectral techniques. The binding affinities of these complexes with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) protein were explored by absorption and fluorescence quenching titrations. The results indicated strong affini...
Source: Nucleosides, Nucleotides and Nucleic Acids - June 4, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Molecular encapsulation of berberine by a modified β-cyclodextrin and binding of host: guest complex to G-quadruplex DNA.
Molecular encapsulation of berberine by a modified β-cyclodextrin and binding of host: guest complex to G-quadruplex DNA. Nucleosides Nucleotides Nucleic Acids. 2019 May 31;:1-16 Authors: Suganthi S, Sivaraj R, Enoch IVMV Abstract The capacity to control quadruplex formation, especially in cancer cells, is captivating and entails a reasonable comprehension of the ligand-G-quadruplex binding. Herein, we report an iminopyrenyl-β-cyclodextrin conjugate interacting with duplex and G-quadrulex DNAs. In addition, the host: guest association of the established G-quadruplex binder, berberine, with th...
Source: Nucleosides, Nucleotides and Nucleic Acids - June 4, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Advancement in the development of heterocyclic nucleosides for the treatment of cancer - A review.
Authors: Mirza AZ Abstract Cancer diseases are widely recognised as an important medical problem and killing millions of people in a year. Chemotherapeutic drugs are successful against cancer in many cases and different compounds, including the analogues of natural substances, may be used for anticancer agents. Nucleoside analogues also have become a necessity for the treatment of cancer diseases. Nucleoside, nucleotide and base analogues have been utilised for decades for the treatment of viral pathogens, neoplasms and in anticancer chemotherapy. This review focuses on the different types of nucleosides and their ...
Source: Nucleosides, Nucleotides and Nucleic Acids - May 30, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

The effect of tumor necrosis factor alpha (-308G/a) and interferon gamma (+874T/a) polymorphisms on susceptibility to coronary heart disease.
Conclusion: This study provides strong evidence supporting the association of TNF-α-308G/A and IFN-γ + 874T/A polymorphisms with the increased risk of CHD. Therefore, these two cytokine polymorphisms may play a role in predisposition to coronary heart disease. PMID: 31140911 [PubMed - as supplied by publisher] (Source: Nucleosides, Nucleotides and Nucleic Acids)
Source: Nucleosides, Nucleotides and Nucleic Acids - May 30, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Molecular docking and spectroscopic studies on the interaction of new fifth-generation antibacterial drug ceftobiprole with calf thymus DNA.
Authors: Shahabadi N, Fili SM, Maghsudi M Abstract The interaction of the cefobiprole drug with calf thymus DNA (ct-DNA) at physiological pH was investigated by UV-visible spectrophotometry, fluorescence measurement, dynamic viscosity measurements, circular dichroism spectroscopy and molecular modeling. The binding constant obtained of UV-visible was 4 × 104 L mol-1. Moreover, the results of circular dichroism (CD) and viscosity measurements displayed that the binding of the cefobiprole to ct-DNA can change the conformation of ct-DNA. Furthermore, thermodynamic parameters indicated that hydrogen...
Source: Nucleosides, Nucleotides and Nucleic Acids - May 16, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Potential epigenomic co-management in rare diseases and epigenetic therapy.
Authors: Nguyen KV Abstract The purpose of this review is to highlight the impact of the alternative splicing process on human disease. Epigenetic regulation determines not only what parts of the genome are expressed but also how they are spliced. The recent progress in the field of epigenetics has important implications for the study of rare diseases. The role of epigenetics in rare diseases is a key issue in molecular physiology and medicine because not only rare diseases can benefit from epigenetic research, but can also provide useful principles for other common and complex disorders such as cancer, cardiovascu...
Source: Nucleosides, Nucleotides and Nucleic Acids - May 15, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Synthesis, spectral studies, DNA binding, photocleavage, antimicrobial and anticancer activities of isoindol Ru(II) polypyridyl complexes.
Authors: Ravi C, Vuradi RK, Avudoddi S, Yata PK, Putta VR, Srinivas G, Merugu R, Satyanarayana S Abstract Three new Ru(II) polypyridyl complexes [Ru(phen)2CIIP]2+ (1) {CIIP = 2-(5-Chloro-3a H-Isoindol-3-yl)-1H-Imidazo[4,5-f][1, 10]phenantholine} (phen = 1, 10 phenanthroline), [Ru(bpy)2CIIP]2+ (2) (bpy = 2, 2' bipyridine) and [Ru(dmb)2CIIP]2+ (3) (dmb = 4, 4'-dimethyl 2, 2' bipyridine) were synthesized and characterized by different spectral methods. The DNA-binding behavior of these complexes was investigated by absorption, emission spectroscopic titration and viscosity measurements, indicating that these three com...
Source: Nucleosides, Nucleotides and Nucleic Acids - May 15, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research

Studies on the Interaction of [SnMe2Cl2(bu2bpy)] Complex with ct-DNA Using Multispectroscopic, Atomic Force Microscopy (AFM) and Molecular Docking.
Authors: Shahabadi N, Momeni BZ, Zendehcheshm S Abstract The interaction of SnMe2Cl2(bu2bpy)complex with calf thymus DNA (ct-DNA) has been explored following, using spectroscopic methods, viscosity measurements, Atomic force microscopy, Thermal denaturation and Molecular docking. It was found that Sn(IV) complex could bind with DNA via intercalation mode as evidenced by hyperchromism and bathochromic in UV-Vis spectrum; these spectral characteristics suggest that the Sn(IV) complex interacts with DNA most likely through a mode that involves a stacking interaction between the aromatic chromophore and the base pairs ...
Source: Nucleosides, Nucleotides and Nucleic Acids - May 5, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research