共查询到20条相似文献,搜索用时 15 毫秒
1.
M. C. Woodle F. I. Raynaud M. Dizik O. Meyer S. K. Huang J. A. Jaeger 《Nucleosides, nucleotides & nucleic acids》2013,32(7-9):1731-1734
Abstract G3139, an 18mer phosphorothioate, down regulates BCL2 and is efficacious in human xenograft tumor models. Studies of pharmacokinetics, toxicology, and influence of formulations on the biological properties of G3139 in mice are described. Bioavailability by s.c. and i.p. saline formulation injections are similar, about 60%. 相似文献
2.
Paul L. Nicklin John Ambler Andrew Mitchelson Deborah Bayley Judy A. Phillips Sarah J. Craig 《Nucleosides, nucleotides & nucleic acids》2013,32(7-9):1145-1153
Abstract Backbone, sugar and pendant-group modifications were shown to influence the anticoagulant properties of a 20-mer oligonucleotide in human plasma in vitro. The pharmacokinetics, tissue-distribution and metabolism of a chimeric oligonucleotide (CGP 69845A), which had reduced anticoagulation properties, were compared with the analogous phosphorothioate oligodeoxynucleotide (CGP 69846A) in a tumour-bearing mouse model. 相似文献
3.
Purshotam Bhan Anila Bhan Mikung Hong John G. Hartwell June M. Saunders Glenn D. Hoke 《Nucleosides, nucleotides & nucleic acids》2013,32(7-9):1195-1199
Abstract ABSTRACT: 3′-Deoxy-(2′-5′) oligonucleotides bind selectively to complementary RNA but not to DNA. 3′-Deoxy-(2′-5′) phosphorothioate ODN chimeras embedded with a short stretch of 3′-5′ phosphorothioate cassette are potent inhibitors of steroid 5-α-reductasc expression with significantly less non-specific interactions in cell culture. 相似文献
4.
Z. S. Cheruvallath A. H. Krotz D. L. Cole V. T. Ravikumar 《Nucleosides, nucleotides & nucleic acids》2013,32(7-9):1625-1628
Abstract Solution phase synthesis of an oligodeoxyribonucleotide phosphorothioate Octamer (5′-TTGGGGTT) using phosphorothioate triester method is reported. 相似文献
5.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):1415-1419
Abstract Activation of 2′-O-substituted ribonucleoside phosphoramidites with various activators during solid-supported synthesis of phosphorothioate oligonucleotides was studied. The Rp:Sp diastereomeric composition of resulting phosphorothioate linkage dependent on pKa of activator utilized for coupling. 相似文献
6.
Isabelle Barber Bernard Rayner Jean-Louis Imbach 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):1083-1085
Abstract The aim of this work was to design phosphorothioate oligonucleotides, the negative charges of which are temporarily masked by a group which facilitates the cellular uptake of these analogues. Then, selective removal of this group by enzymes normally present in the cells will deliver intracellularly the intact charged phosphorothioate oligomers able to hybridize to their complementary RNA targets and to elicit RNase H activity. 相似文献
7.
Takeshi Wada Naotake Kobayashi Toshiya Mori Mitsuo Sekine 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):351-364
Abstract Diastereoselective formation of internucleotidic phosphorothioate triester bonds was achieved by use of 3-(imidazol-1-ylmethyl)-4′,4″-dimethoxytrityl (IDTr) as a 5′-hydroxyl protecting group in the phosphotriester approach. After removal of all the protecting groups, stereochemistry of the major product was determined as the Spconfiguration by enzymatic digestion. 相似文献
8.
F. Eckstein 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):77-79
Abstract The synthesis of Rp- and Sp-d (GGsAATTCC), an octanucleotide containing the recognition sequence for the restriction endonuclease Eco R1 as well as a phosphorothioate group at the cleavage site is described. Only the Rp-diastereomer is a substrate for Eco R1. Viral DNA, containing exclusively phosphate groups in the (+)strand, and phosphorothioate groups 5′-to deoxyadenosine in the (-)strand yields nicked DNA on cleavage by Eco R1 as an isolatable intermediate. Other restriction enzymes show a similar pattern of hydrolysis. - The influence of phosphorothioate groups on the B Z conformational change is demonstrated on phosphorothioate analogues of d(C-G)4 and d(G-C)4. 相似文献
9.
Alessandra Eleuteri Zacharia S. Cheruvallath Daniel C. Capaldi Douglas L. Cole Vasulinga T. Ravikumar 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1803-1807
Abstract An efficient solution phase synthesis of deoxyribonucleoside phosphorothioate dimers utilizing phosphoramidite approach is described. Diethyldithiocarbonate disulfide (DDD) was found to be an efficient sulfurizing reagent in the conversion of phosphite triesters to phosphorothioate triesters. 相似文献
10.
Zacharia S. Cheruvallath Tadeusz K. Wyrzykiewicz Douglas L. Cole Vasulinga T. Ravikumar 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):1191-1194
Abstract The emergence of antisense and antigene oligonucleotides as potential sequenceselective inhibitors of gene expression is evidenced by the growing number of ongoing clinicals trials against a variety of diseases. First generation antisense therapeutics utilize a uniformly modified oligodeoxyribonucleotide phosphorothioate where one non-bridging oxygen atom is formally replaced by sulfur, because natural DNA is unstable towards extra- and intracellular enzymes. Phosphoramidite chemistry has been widely used for the synthesis of phosphorothioate oligonucleotides because of its potential for automation, high coupling efficiency, ease of site-specific thioate linkage incorporation, and ready scalability. The large scale solid-supported synthesis of phosphorothioates is presently carried out by initial formation of the internucleotidic phosphite linkage followed by sulfurization of the phosphite triester to phosphorothioate using the Beaucage reagent. The resulting O,O-linked phosphorothioate diester linkage in the oligonucleotide is a chiral functional group. For a typical 20-mer there are 524,288 (219) possible diastereoisomers. Separation and individual quantification of this number of diastereomers is currently not feasible. In addition, the best reported methods for stereocontrolled synthesis of phosphorothioate oligomers are not presently useful for drug synthesis; that is, since net 100% enantiomeric excess is not achieved in the coupling step, the oligomeric product still consists of the same mixture of Sp and Rp diastereomers, except that the levels of all but one isomer are reduced to low individual levels. As a result, even a small change in the and Sp phosphorothioate diesters, due to racemization during coupling, indicating that the overall synthetic process is stereo reproducible and under inherent process control. 相似文献
11.
Robert J. Suhadolnik Bernard Lebleu Wolfgang Pfleiderer Ramamurthy Charubala David C. Montefiori William M. Mitchell 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):987-990
Abstract Chemically and enzymatically synthesizeddiastereomeric 2′,5′- phosphorothioate dimer, trimer and tetramer cores and their 5′ - mono- and triphosphates demonstrate marked differences in their ability to bind to and activate RNase L from L929 cell extracts in radiobinding, core-cellulose and rRNA cleavage assays1,2 (Fig. 1). These are the first 2-5A cores that are able to bind to and activate Mase L. The enzymatically synthesized 2′,5′- phosphorothioate dimer and trimer 5′-triphosphates can also bind to and activate mase L1. 相似文献
12.
Takanori Miyashita Kohei Yamada Kazuhiko Kondo Kenya Mori Kazuo Shinozuka 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):955-962
Abstract A facile synthetic method of a phosphorothioate dimer block was investigated. Dinucleoside phosphite triester intermediates were obtained in one-pot synthesis by the coupling of a protected nucleoside bearing free 5′-OH and a protected nucleoside bearing free 3′-OH in the presence of phosphorous trichloride (PCl3) and 1,2,4-triazole. The intermediates were easily sulfurized to afford the desired phosphorothioate dimer blocks in 33-64% overall yields. 相似文献
13.
Maria Koziokiewicz Edyta Gendaszewska Maria Maszewska 《Nucleosides, nucleotides & nucleic acids》2013,32(7-9):1677-1682
Abstract Stability of oligo(nucleoside phosphorothioate)s (PS-oligos) in HUVEC (human umbilical vein endothelial cells) has been studied. Cytosolic fraction of HUVEC possesses 3′-exonucleolytic activity which is responsible for degradation of natural oligomers and PS-oligos. The enzyme is Rp-specific, i.e. it cleaves internucleotide phosphorothioate function of Rp- and not Sp-configuration at phosphorus atom. 相似文献
14.
Alessandra Eleuteri Daniel C. Capaldi Douglas L. Cole Vasulinga T. Ravikumar 《Nucleosides, nucleotides & nucleic acids》2013,32(3):475-483
Abstract Use of fully protected trimeric phosphoramidite synthons in the synthesis of oligonucleotide phosphorothioate shows a substantial reduction (>85%) in (n-1)-mer content as compared to oligomers synthesized through coupling of standard phosphoramidite monomers. A 20-mer oligodeoxyribonucleotide phosphorothioate which is in phase I clinical trials was chosen as an example for the studies. 相似文献
15.
Anthony DiRenzo Susan Grimm Kurt Levy Peter Haeberli Lara Maloney Nassim Usman 《Nucleosides, nucleotides & nucleic acids》2013,32(11-12):1687-1700
Abstract A systematic study of the catalytic activity and nuclease stability of selectively modified hammerhead ribozymes has resulted in the identification of a generic motif containing 5 ribose residues and 31 2′- modified sugars (1). This substructure has been further elaborated to include phosphorothioate linkages. Although oligodeoxyribonucleotides containing phosphorothioate linkages have been studied extensively, similarly substituted RNA molecules or ribozymes have not been explored at-length. The synthesis and purification of these ribozymes is discussed (2). 相似文献
16.
17.
Abstract Synthesis of unprotected dinucleoside phosphorofluoridate and phosphorofluoridothioates from the corresponding phosphorothioate and phosphorodithioate derivatives is described. 相似文献
18.
Andrei Guzaev Brunel Boyode Guity Balow Muthiah Manoharan 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):1389-1390
Abstract A novel synthesis of 5′-radiolabeled oligonucleotides is described. The labeling is carried out by the phosphoramidite method with the aid of building block 1. The feasibility of the method is demonstrated by preparation of 5′-radiolabeled 3′-phosphorylated dodecathymidylate phosphorothioate. 相似文献
19.
Summary The synthesis of phosphorothioate analogues of oligonucleotides by the oxidation of deoxyadenosine 3,5-bisphosphorothioate (3) was attempted. Cyclization of3 is much more efficient than oligomerization under all the conditions investigated. However, a preformed oligonucleotide carrying a 5-terminal phosphorothioate group undergoes efficient chain-extension when oxidized in the presence of3. 相似文献
20.
A. Laurent F. Debart-Vasseur J.-L. Imbach B. Rayner 《Nucleosides, nucleotides & nucleic acids》2013,32(7-9):1765-1766
Abstract The synthesis of two oligonucleoside phosphorothioate and methyl-phosphonate analogs functionalized with a fluorogenic tag is described. The fluorescent conjugate formation is demonstrated in cell culture medium, cell extracts and in human fibroblasts. 相似文献