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1.
Jin-Young Kim Seong-Cheol Park Jong-Kook Lee Sang Joon Choi Kyung-Soo Hahm Yoonkyung Park 《PloS one》2012,7(11)
An antibacterial protein (about 12 kDa) was isolated from human amniotic fluid through dialysis, ultrafiltration and C18 reversed-phase HPLC steps. Automated Edman degradation showed that the N-terminal sequence of the antibacterial protein was NH2-Ile-Gln-Arg-Thr-Pro-Lys-Ile-Gln-Val-Tyr-Ser-Arg-His-Pro-Ala-Glu-Asn-Gly-. The N-terminal sequence of the antibacterial protein was found to be identical to that of β2-microglobulin, a component of MHC class I molecules, which are present on all nucleated cells. Matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) revealed that the molecular mass of the antibacterial protein was 11,631 Da. This antibacterial protein, β2M, possessed potent antibacterial activity against pathogenic bacteria. Specially, antibacterial activity was observed in potassium buffer, and potassium ion was found to be critical for the antibacterial activity. Interestingly, the antibacterial action of β2M was associated with dissipation of the transmembrane potential, but the protein did not cause damage to the membrane that would result in SYTOX green uptake. In addition, stimulation of WISH amniotic epithelial cells with the bacterial endotoxin lipopolysaccharide (LPS) induced dose-dependent upregulation of β2M mRNA expression. These results suggest that β2M contributes to a self-defense response when amniotic cells are exposed to pathogens. 相似文献
2.
Abstract 2′-Azido-2′-deoxyuridine and 2′-azido-2′-deoxycytidine were evaluated for their inhibitory activity against ribonucleotide reductase and for subsequent cell growth inhibition. Their mono-and di-phosphates were synthesized and their inhibitory activities against the reductase were also determined in a permeabilized cell system, along with the two nucleosides. The results of the present study identify the first phosphorylation step involved in the conversion of the two azidonucleosides to the corresponding diphosphates to be rate-limiting in the overall activation. 相似文献
3.
Lak Shin Jeong Hyung Ryong Moon Su Jeong Yoo Sun Nan Lee Hee-Doo Kim Moon Woo Chun 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):571-572
Abstract L-2′-Deoxy-2′-up-fluoro-4′-thionucleosides were efficiently synthesized from D-xylose via L-4-thioarabitol derivative as a key intermediate and evaluated for antiviral activities against HIV-1, HSV-1,2 and HBV. 相似文献
4.
5.
Abstract 5-Ethyl-2′-deoxyurldine (EDU) is phosphorylated to a much greater extent by herpes simplex virus (HSV)-infected Vero cells than by mock-infected cells. Within the infected cells, EDU is preferentially incorporated into viral DNA and more inhibitory to viral than cellular DNA synthesis 相似文献
6.
Tokumi Maruyama Kunihiko Utzumi Yoshiko Sato Douglas D. Richman 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):527-537
Abstract 3′,5′-Di-O-protected 6-chloropurine arabinoside 4b was treated with diethylaminosulfur trifluoride (DAST) and subsequently deprotected with pyridinium p-toluenesulfonate to give 6-chloropurine 2′-deoxy-2′-fluororiboside 6a. The displacement with nucleophile afforded the 6-substituted congener 6b-e. Treatment of 5′-O-protected 6-chloropurine arabinoside 3c with DAST gave lyxoepoxide 7. 相似文献
7.
Takanori Miyashita Noriyuki Ashida Kazuhiko Kondoh Shinji Sakata Haruhiko Machida Akihiro Fujii 《Nucleosides, nucleotides & nucleic acids》2013,32(2-4):495-513
Abstract For the purpose of improvement of the in vivo antitumor activity of 2′-deoxy-2′-methylidenecytidine (DMDC, 1), we synthesized its various acyl and benzyl derivatives and evaluated them for their antitumor activity against P388 murine leukemia in mice. In terms of minimum effective dose (30% increase in life span), 5′-O-stearoyl DMDC showed two-fold higher antitumor activity than DMDC on a molar basis, when intraperitoneally (i.p.) administered to mice once a day. The antitumor activities of some other acyl derivatives were almost comparable to that of DMDC, while benzyl derivatives had no antitumor activity. Results on the hydrolysis of 5′-O-acyl derivatives by porcine liver esterase showed that at least these derivatives should not be resistant to enzymatic hydrolysis for exhibiting antitumor activity. After either an i.p. or oral dose of 3′-O-benzyl DMDC, very low concentrations of blood DMDC were seen compared with those after administration of DMDC, suggesting that the inactivity of benzyl derivatives as prodrugs was due to the minimal level of DMDC in circulation after administration. 相似文献
8.
P. Herdewijn R. Charubala R. Pauwels E. De Clercq W. Pfleiderer 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):443-444
Abstract One of the most important mediators in the mode of action of interferon is the (2′-5′)(A)n synthetase-RNase L pathway. The 2′-5′oligoadenylates (2–5A), synthesized from ATP, activate a pre-existing endonuclease that cleaves single-stranded RNA. The biological activity of 2–5A is rapidly lost due to cleavage of the 2′-5′ internucleotide bond by a specific 2′-5′-phosphodiesterase starting at the 3′end. This rapid cleavage and the poor uptake of 2–5A in intact cells limit the use of 2–5A as an antiviral or antineoplastic agent. Although several modified 2–5A analogues have been synthesized in order to improve the enzymatic stability, only few have proven to be resistant to degradation and still able to activate the 2–5A dependent endonuclease. 1-4 On the other hand, relative drastic methodology such as calcium coprecipitation, microinjection and liposome encapsulation5 has been used to introduce 2–5A into intact cells. Here, we present the synthesis and biological activity of oligoadenylates in which one or more adenosine residues were replaced by 9-(3-azido-3-deoxy-6-D-xylofuranosyl)adenine or 9-(3-amino-3-deoxy-D-xylofuranosyl)adenine. The oligonucleotides were synthesized by the phosphotriester method with triisopropylbenzenesulfonyl-chloride in the presence of N-methylimidazole as the condensing agent. The p-nitrophenylethyl group was used as the protecting group for the 2′-hydroxylfunction .(carbonate), the internucleotide linkage (phosphate ester) and the exocyclic amino groups of the heterocyclic base (carbamate). Bis(p-nitrophenylethy1)phosphoromonochloridate was used to phosphorylate the 5′-hy-droxyl group. All these blocking groups were removed with DBU in pyridine. 相似文献
9.
Harry Ford Jr. John S. Driscoll Maqbool Siddiqui James A. Kelley Hioraki Mitsuya Takuma Shirasaka 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):213-234
Abstract The 2′-β-fluoro analogue of 2′,3′-dideoxyguanosine has been prepared by two synthetic routes. This compound and two analogues have anti-HIV activity in at least two of three host cell systems used (ATH8, CEM, PBL). These compounds, as well as their ddGuo parents, have been characterized with regard to their acid-stabilities, octanol-water partition coefficients, and enzyme substrate properties for adenosine deaminase and purine nucleoside phosphorylase. F-ddGuo analogues are less potent but more stable than their non-fluorinated parent compounds. 相似文献
10.
Shin HongKang A. K. Sinhababu Moo J. Cho 《Nucleosides, nucleotides & nucleic acids》2013,32(6):1089-1098
Abstract Bis(pivaloyloxymethyl) ester of 2′-azido-2′-deoxyuridine 5′-monophosphate was prepared as a prodrug to generate 2′-azido-2′-deoxyuridine 5′-diphosphate inside the cell. A synthetic route utilizing stannyl phosphate was adopted in the preparation. The prodrug was evaluated for cell growth inhibition against a variety of tumor cell lines along with 2′-azido-2′-deoxyuridine and 2′-azido-2′-deoxycytidine. 相似文献
11.
Lea Messini Kamal N. Tiwari John A. Montgomery John A. Secrist III 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):683-685
Abstract Coupling of 1-O-acetyl-2-deoxy-3,5-di-O-toluoyl-4-thio-d-ribofuranose with 6-chloropurine and 2,6-dichloropurine gave a mixture of 9α and 9β anomers as major products. These anomers were separated and converted to 2′-deoxy-4′-thio analogues of adenosine, inosine, guanosine, 2-amino-adenosine, and 2-chloro adenosine as well as their α-anomers. 相似文献
12.
Kamal N. Tiwari John A. Secrist III John A. Montgomery 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1819-1828
Abstract 1,2,3,5-Tetra-O-acetyl-4-thio-D-riboruranose, prepared from 2,3,5-tri-O-benzyl-D-ribofuranose in four steps, was converted to the corresponding 2-chloroadenine nucleoside (8), which was deoxygenated to obtain 2-chloro-2′-deoxy-4′-thioadenosine (12). This is the first report of a 2′-deoxy-4′-thioribonucleoside of a purine rather than a pyrimidine. These novel nucleosides (8 and 12) were cytotoric to several human tumor cell lines in culture. 相似文献
13.
P. P. Torrence D. Alster S. Huss G. Gosaelin J.-L. Imbach 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):521-522
Abstract Sequential substitution of xyloadenosine into the trimeric and tetrameric 2–5A cores1 allows evaluation of the importance of the 3′ hydroxyl groups to 2′5′-phosphodiesterase (PDE) activity. 相似文献
14.
Maxim Jasko Alexander Shipitsin Elena Shirokova Alexander Krayevsky Bruce Polsky Penny Baron 《Nucleosides, nucleotides & nucleic acids》2013,32(8):879-893
Abstract 5′-Phosphonates of natural 2′-deoxynucleosides and ribonucleosides were synthesized by condensation of 3′-O-acylated 2′-deoxynucleosides or 2′,3′-substituted (2′,3′-O-isopropylidene, 2′,3′-O-methoxymethylene or 2′,3′-O-ethoxymethylene) ribonucleosides. As condensing agents, either N,N′-dicyclohexylcarbodiimide or 2,4,6-triisopropylbenzenesulphonyl chloride were used. Nucleoside 5′-ethoxycarbonylphosphonates were converted into corresponding nucleoside 5′-aminocarbonylphosphonates by action of ammonia in methanol or aqueous ammonia. 5′-Hydrogenphosphonothioates of thymidine and 3′-deoxythymidine were obtained by reaction of phosphinic acid in the presence of pivaloyl chloride with 3′-O-acetylthymidine or 3′-deoxythymidine, respectively, followed by addition of powedered sulfur. 5′-O-methylenephosphonates of thymidine and 2′-deoxyadenosine were prepared by intramolecular reaction of corresponding 3′-O-iodomethylphosphonates under basic conditions. All compounds were tested for inhibition of several viruses, including HSV-2 and CMV, but showed no activity. A few compounds insignificantly inhibited HIV-1 reproduction. Thymidine 5′-hydrogenphosphonate neutralized anti-HIV action of 3′-azido-3′-deoxythymidine (AZT) and it indirectly showed that even some nucleoside 5′-phosphonates could be partly hydrolyzed in cell culture to corresponding nucleosides. 5′-Phosphonates of modified 2′-deoxynucleosides in which one group in a phosphate residue is substituted for hydrogen, alkyl or other groups, have shown to be potent biologically 相似文献
15.
Jens Haas Thea Mueller-Kuller Stefan Klein Joachim W. Engels 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):865-868
We recently reported that a 1′-deoxy-1′-(4,6-difluoro-1H-benzimidazol-1-yl)-2′-(β-aminoethyl)-β-d-ribofuranose nucleoside appears to be a universal nucleoside which does not differentiate between the four natural nucleosides A, C, G, and U in duplexes. Moreover, ribozymes modified with this nucleoside analog showed a better or at least equal catalytic activity relative to Watson-Crick mismatches.[ 1 ] Due to these data, we investigated the ability of this compound to tolerate Watson-Crick mismatches in order to avoid HIV escape mutations in RNA interference. The influence of this nucleoside analog on siRNA efficiency was analyzed with a proven siRNA targeting GFP. 相似文献
16.
B. Ts. Shagdarova A. V. Il’ina V. P. Varlamov 《Applied Biochemistry and Microbiology》2016,52(2):222-225
A number of alkylated (quaternized) and acylated derivatives of low–molecular weight chitosan were obtained. The structure and composition of the compounds were confirmed by the results of IR and PMR spectroscopy, as well as conductometric titration. The effect of the acyl substituent and the degree of substitution of N-(2-hydroxy-3-trimethylammonium) propyl fragment appended to amino groups of the C2 atom of polymer chains on antibacterial activity against typical representatives of gram-positive and gramnegative microorganisms (Staphylococcus epidermidis and Escherichia coli) was studied. The highest activity was in the case of N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride (HTCC) with the maximal substitution (98%). The minimal inhibitory concentration of the derivative was 0.48 μg/mL and 3.90 μg/mL for S. epidermis and E. coli, respectively. 相似文献
17.
Thazha P. Prakash Nishant Naik Namir Sioufi Balkrishen Bhat Eric E. Swayze 《Nucleosides, nucleotides & nucleic acids》2013,32(10):902-910
In a search to identify chemical modifications to improve the properties of siRNA, we have investigated the effect of the 2 ′-O-methyl-2-thiouridine modification on the biological activity of siRNA. Our results indicate that judicious placement of 2 ′-O-methyl-2-thiouridine residues could lead to modified siRNA with activity in mammalian cells. 相似文献
18.
Rakesh Kumar Edward E. Knaus Leonard I. Wiebe 《Nucleosides, nucleotides & nucleic acids》2013,32(6):1219-1228
Abstract Reaction of the 5′-O-t-butyldimethylsilyl derivatives of thymidine and 2′-deoxyuridine with the Vilsmeier reagent (POCI3/DMF), and removal of the t–butyldimethylsilyl protecting group, afforded 3′-O-formylthymidine (5) and 3′-O-formyl-2′-deoxyuridine (6), respectively. In vitro evaluation, determined as the ability of the test compound to inhibit HIV induced cytopathogenicity in CEM cells, indicated that 5 was moderately active, whereas 6 was inactive. 相似文献
19.
Abstract The synthesis of two nucleosides, 1-(3-azido-2,3-dideoxy-β-D-ribofuranosyl)-5-iodo- and -5-bromo-2(1H)-pyrimidinone, 1a and 1b, is described. Neither 1a nor 1b exhibited significant inhibition of T, lymphocyte growth. However, both compounds were unable to protect T, lymphocytes from the cytopathic effects of HIV. 相似文献
20.
Victor E. Marquez Lak S. Jeong Marc C. Nicklaus Cliff George 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):555-558
Abstract The efficient DAST fluorination of deoxy-4′-thiopyrimidine nucleosides is reported. The cytidine analogue 3b was marginally effective against HIV. 相似文献