Disease relevance of trioxido-thioxo-phosphorane

• The phosphorothioate stereoselectivity of the corresponding steps of phage Mu transposition and HIV DNA integration matches that of Tn10 reaction, indicating a common mode of substrate-active site interactions for this class of DNA transposition reactions [1].
• We studied the effects of antisense phosphorothioate oligodeoxynucleotide (ODN) against this enzyme using gene transfer mediated by a hemagglutinating virus of Japan (HVJ)-liposome complex intraluminally delivered to inhibit the intimal hyperplasia [2].
• Local administration of p65 antisense phosphorothioate oligonucleotides abrogated clinical and histological signs of colitis and was more effective in treating TNBS-induced colitis than single or daily administration of glucocorticoids [3].
• To determine whether the expression of uPAR and alpha v were linked, alpha v synthesis in the metastatic melanoma cells was suppressed using alpha v antisense phosphorothioate oligonucleotides [4].
• To test the hypothesis that inhibition of the expression of this key enzyme can inhibit intimal hyperplasia, we studied the effect of antisense phosphorothioate oligodeoxynucleotides (ODN) against cdk 2 kinase administered by intraluminal delivery using hemagglutinating virus of Japan (HVJ)-liposome-mediated transfer [5].

Psychiatry related information on trioxido-thioxo-phosphorane

• Increasing oligo length from 20nt to 30nt increases phosphorothioate oligo efficiency over long reaction times in vivo, but decreases efficiency during short in vitro assays [6].
• This study investigated the effects of ICV-administered antisense phosphorothioate oligonucleotides, directed against the CRF mRNA, on feeding behavior and body weight in rats [7].

High impact information on trioxido-thioxo-phosphorane

• We examined phosphorothioate stereoselectivity at the scissile position for all four reaction steps catalyzed by the Tn10 transposase [1].
• Soluble fibrinogen, a natural ligand for Mac-1, was an excellent competitor of the binding of a phosphorothioate oligodeoxynucleotide to both TNF-alpha-activated and nonactivated PMNs [8].
• We have studied the interactions of phosphodiester and phosphorothioate oligodeoxynucleotides with Mac-1 (CD11b/CD18; alpha M beta 2), a heparin-binding integrin found predominantly on the surface of polymorphonuclear leukocytes (PMNs), macrophages and natural killer cells [8].
• Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice [3].
• Treatment of human tumor cells with appropriate phosphorothioate antisense oligodeoxynucleotides led to specific inhibition of C-raf kinase gene expression in cell culture and in vivo at well-tolerated doses [9].

Chemical compound and disease context of trioxido-thioxo-phosphorane

• This effect is oligomer length-dependent, and the ability of phosphorothioate homopolymers of thymidine of variable lengths to cause the release of cytochrome c from isolated mitochondria of 518A2 melanoma cells can be correlated with their ability to interact with VDAC [10].
• 2'-Deoxyadenosine 5'-O-(1-thiotriphosphate) (dATP[alpha S]) was introduced into the 3' ends of DNA restriction fragments with Escherichia coli DNA polymerase I to give phosphorothioate internucleotide linkages [11].
• The effects of the phosphorothioate agent, WR-2721, have been investigated with respect to the biotransformations of ormaplatin in the Fischer 344 rat bearing a transplanted fibrosarcoma [12].
• This study was designed to assess the efficacy of a new antimelanoma therapeutic strategy that relies on the use of a c-myc antisense 15-mer phosphorothioate oligodeoxynucleotide ([S]ODN), in combination with cisplatin (cis-diamminedichloroplatinum; DDP), which is currently used in the clinical management of melanoma patients [13].
• We used phosphorothioate antisense oligonucleotides (ASO) targeted against Plk1, together with paclitaxel, carboplatin, and Herceptin, for the treatment of breast cancer cells to identify conditions for enhanced drug sensitivity [14].

Biological context of trioxido-thioxo-phosphorane

• Although much is known about the stereochemical course of reactions at saturated carbon, phosphate and thiophosphate esters whose ligands to phosphorus are also tetrahedrally disposed, are capable in principle of revealing sterochemical information about events at the active site of enzymes that transform such substrates [15].
• DNA and RNA sequence determination based on phosphorothioate chemistry [16].
• Octamer-dependent activation of a reporter plasmid or NF-kappa B-dependent activation of the human immunodeficiency virus (HIV) enhancer was inhibited when the appropriate phosphorothioate oligonucleotide was added to a transiently transfected B cell line [17].
• Selective strand cleavage is achieved through alkylation to form the hydrolytically labile phosphorothioate triester [16].
• Inhibition of sequence-specific DNA-binding proteins was achieved with double-stranded (ds) phosphorothioate oligonucleotides that contained octamer or kappa B consensus sequences [17].

Anatomical context of trioxido-thioxo-phosphorane

• Additionally, because both steps are strongly inhibited by the RP phosphorothioate diastereomer, but not by SP, the spliceosome probably shifts between two active sites in catalysis of the two steps [18].
• We could suppress GATA-3 expression in interleukin (IL)-4-producing T cells in vitro and in vivo by an antisense phosphorothioate oligonucleotide overlapping the translation start site of GATA-3, whereas nonsense control oligonucleotides were virtually inactive [19].
• We have used antisense phosphorothioate oligonucleotides to define the role played by proliferating cell nuclear antigen (PCNA) in neointimal accumulation of smooth muscle cells in a rat carotid artery injury model [20].
• Sequence-independent inhibition of in vitro vascular smooth muscle cell proliferation, migration, and in vivo neointimal formation by phosphorothioate oligodeoxynucleotides [21].
• Using phosphorothioate FITC-labeled ODN, we transfected carotid artery using the HVJ-liposome method [5].

Associations of trioxido-thioxo-phosphorane with other chemical compounds

• An antisense phosphorothioate (S)-oligonucleotide to a sequence in the intervening (I) region of the gamma 2b immunoglobulin (Ig) heavy chain gene inhibits Ig secretion by B cells stimulated with lipopolysaccharide (LPS) or LPS plus interleukin 4 [22].
• Incorporation of four phenoxazine bases into a previously optimized C-5 propyne pyrimidine modified 7-mer phosphorothioate oligonucleotide targeting SV40 large T antigen enhanced in vitro binding affinity for its RNA target and redirected RNAse H-mediated cleavage as compared with the 7-mer C-5 propynyl phosphorothioate oligonucleotide (S-ON) [23].
• Additional experiments using a 514-nucleotide-long RNA substrate demonstrated the capacity of complementary phosphodiester- and phosphorothioate-linked oligodeoxynucleotides (but not ones containing methylphosphonate, phosphoro-N-morpholidate, or phosphoro-N-butylamidate linkages) to serve as RNase H targets when hybridized to an internal RNA site [24].
• By using a human cell-free system capable of nucleotide excision repair, a synthetic substrate consisting of a plasmid containing four thymidine dimers at unique locations, and deoxyribonucleoside 5'-[alpha-thio]triphosphates for repair synthesis, we obtained DNA fragments containing repair patches with phosphorothioate linkages [25].
• We have further explored the sequence requirements of this non-AS effect and determined that phosphorothioate oligonucleotides containing at least two sets of three or four consecutive guanosine residues inhibit SMC proliferation in vitro and ex vivo [26].

Gene context of trioxido-thioxo-phosphorane

• Phosphorothioate oligodeoxynucleotides bound to the cell surface, as demonstrated by fluorescence-activated cell-sorter analyses (FACS), and perturbed receptor activation in the presence and absence of cognate ligands, EGF (EGFR) and vascular endothelial growth factor (flk-1), in phosphorylation assays [27].
• An MDM2 antisense phosphorothioate oligodeoxynucleotide has been identified that effectively inhibits MDM2 expression in tumor cells containing MDM2 gene amplifications [28].
• A phosphorothioate-protected 17-mer directed against the initiation of translation sites of the p42 and p44 MAPK isoform mRNAs was introduced into cultured cardiac myocytes by liposomal transfection [29].
• Here we have used specific phosphorothioate oligonucleotides targeted against the two major isoforms, JNK1 and JNK2, to discriminate their roles in EGF-induced transformation [30].
• Functional experiments were performed on purified HPCs treated with phosphorothioate antisense oligodeoxynucleotides to Id2 or TAL1 mRNA [31].

Analytical, diagnostic and therapeutic context of trioxido-thioxo-phosphorane

• Nevertheless, preclinical animal studies now suggest that phosphorothioate ODNs may be more permeable in certain animal tissues than in cell culture, raising hopes that antisense mechanisms can be exploited pharmacologically [32].
• Phosphodiester oligonucleotides are nuclease sensitive, and the more nuclease-resistant phosphorothioate oligonucleotides are now in common use in the laboratory and have entered clinical trials [33].
• As these phosphorothioate-containing polymers are stable to degradation by nucleases and the sulfur atom confers many favourable chemical properties, several applications in molecular biology have been developed, including new methods for site-directed mutagenesis and DNA sequencing [34].
• For 7 consecutive days, beginning 1 day after tumor cell transplantation, the mice were given either a DNA phosphorothioate oligonucleotide complementary to c-myc codons 1-5 (myc6) or other c-myc-related oligonucleotides at a dose of 0.76 mg per day subcutaneously [35].
• Selective inhibition of endogenous MDGI expression in MEC by antisense phosphorothioate oligonucleotides suppresses appearance of alveolar end buds and lowers the beta-casein level in organ cultures [36].

References