An investigation of several deoxynucleoside phosphoramidites useful for synthesizing deoxyoligonucleotides

McBride, L J; Caruthers, Marvin H.

doi:10.1016/s0040-4039(00)81376-3

Cited by 541 publications

(236 citation statements)

References 5 publications

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“…We used a second strategy to generate a construct with a stronger stability against ribonucleases by the standard phosporamidite chemistry 16,17 as described A siRNA targeting β-galactosidase (β-Gal-128) bearing a motif eliciting interferon production was also used. 18 Stock solutions of all siRNAs were prepared by re-suspension of the lyophilized product in RNAse-free water and stored at -20ºC until use.…”

Section: Animalsmentioning

confidence: 99%

Selective siRNA-mediated suppression of 5-HT1A autoreceptors evokes strong anti-depressant-like effects

et al. 2011

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Depression is a major health problem worldwide. Most prescribed antidepressants, the selective serotonin reuptake inhibitors (SSRI) show limited efficacy and delayed onset of action, partly due to the activation of somatodendritic 5-HT 1A -autoreceptors by the excess extracellular serotonin (5-HT) produced by SSRI in the raphe nuclei. Interestingly, intranasal C-1A-siRNA administration produced the same effects, thus opening the way to the therapeutic use of C-1A-siRNA. Hence, C-1A-siRNA represents a new approach to treat mood disorders, as monotherapy or in combination with SSRI.3

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Section: Animalsmentioning

confidence: 99%

Selective siRNA-mediated suppression of 5-HT1A autoreceptors evokes strong anti-depressant-like effects

et al. 2011

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“…Oligonucleotides were prepared on an Applied Biosystems ABI 380B DNA synthesiser using the phosphordmidite method (McBride and Caruthers, 1983) and purified by reversedphase HPLC and Sephadex gel filtration (Brown and Brown, 1991 a. b …”

Section: Chemical Synthesismentioning

confidence: 99%

Anthracycline binding to DNA

Leonard

Brown

Hunter

1992

European Journal of Biochemistry

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Crystallographic methods have been applied to determine the high-resolution structure of the complex formed between the self-complementary oligonucleotide d(TGTACA) and the anthracycline antibiotic 4-epiadriamycin. The complex crystallises in the tetragonal system, space group P4,212 with c1 = 2.802 nm and c = 5.293 nm, and an asymmetric unit consisting of a single D N A strand, one drug molecule and 34 solvent molecules. The refinement converged with an R factor of 0.17 for the 2381 reflections with F a 3oF in the resolution range 0.70-0.14 nm. Two asymmetric units associate such that a distorted B-DNA-type hexanucleotide duplex is formed incorporating two drug molecules that are intercalated at the TpG steps. The amino sugar of 4'-epiadriamycin binds in the minor groove of the duplex and displays different interactions from those observed in previously determined structures. Interactions between the hydrophilic groups of the amino sugar and the oligonucleotidc are all mediated by solvent molecules. Ultraviolet melting measurements and comparison with other anthracycline-DNA complexes suggest that these indirect interactions have a powerful stabilising effect on the complex.Nucleic acids and the proteins that interact with them are primary targets for chemotherapy (Fisher and Aristoff, 1988). The development of new antibiotics and anticancer agents is guided by knowledge of how such compounds interact with specific biochemical targets and thereby exert their influence.Anthracycline antibiotics are of particular interest as potent antitumour agents which bind to both DNA and the DNAbinding protein topoisomerase 11. It has been demonstrated that interactions with DNA are primarily responsible for the biological activity of anthracyclines (Valentini et al., 1985). Despite the fact that these antibiotics have been used clinically for the treatment of ccrtain cancers, they possess serious side effects, most notably cardiotoxicity. It is important to characterise the structures formed betwecn anthracycline antibiotics and DNA in order to understand the precise nature of the molecular intcractions. The structural information may then facilitate the rational design of improved, more selective anticancer, antibiotic or anti-viral agents.The two most-studied anthracyclines are adriamycin and daunomycin. Various methods have been used to study the interactions of these molecules with D N A (Chaires. 1990). Thesc include thooretical studies (Chen ct al., 1985, Pullman, 1987, 1991 and techniques such as DNA footprinting , Skavobogaty et al., 1988a, both of which provide evidence for preferential binding to certain DNA sequences. Of note is thc observation that thesc compounds recognise and bind to three consecutive base pairs. Rcceiitly, a series of X-ray structures have appeared which

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“…While still cold, the reaction mixture was poured into saturated aqueous sodium bicarbonate and the organic layer was then washed with brine and dried over sodium sulfate. Evaporation of the solvent followed by fractional distillation of the crude liquid from calcium hydride afforded Preparation of bis-(morpholino)methoxyphosphine (6) To 744 g (50 mmol) of methyldichlorophosphite in 200 ml of diethylether at -10°C under a nitrogen atmosphere was added 26.0 g (300 mmol, 6 eq) of morpholine over 1 h. The reaction mixture was allowed to warm to room temperature and stirred an additional 16 h. Removal of the amine salt by filtration and evaporation of the solvent gave a colorless liquid. The crude material was fractionally distilled from calcium hydride to afford 9.5 g (81%) To a mixture of 544 mg (1.0 mmol) of la and 86 mg (0.5 mmol, 0.5 eq) of 9 in 5 ml of dry dichloromethane under a nitrogen atmosphere was added 282 mg (1.1 mmol, 1.1 eq) of phosphine 4.…”

Section: Reagents and Solventsmentioning

confidence: 99%

“…Although these phosphoramidites can be prepared by existing methods (5,6) from the appropriately protected deoxynucleosides la-d, the chlorophosphines 2 and 3 used in forming 7a-d and 8a-d, respectively, are difficult to prepare and easily react with trace amounts of water. Moreover, the high reactivity of 2 and 3 and the concomitant production of insoluble amine hydrochloride salts preclude their use for any strategy involving the in situ generation of deoxynucleoside phosphoramidites for deoxyoligonucleotide synthesis on solid supports (7).…”

Section: Introductionmentioning

confidence: 99%

In situactivation of bis-dialkylaminophosphines—a new method for synthesizing deoxyoligonucleotides on polymer supports

1984

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Deoxynucleoside phosphoramidites can be prepared in good yield from deoxynucleosides, bis-dialkylaminophosphines, and the corresponding dialkylamine hydrotetrazolide or tetrazole as catalysts. These phosphoramidites generated in situ lead to the direct synthesis of deoxyoligonucleotides on polymer supports. INTRODUCTIONThe current phosphite triester methodology for deoxyoligonucleotide synthesis requires the condensation of deoxynucleoside phosphoramidites 7a-d or 8a-d, activated by tetrazole, with the 5'-hydroxyl group of a deoxynucleoside or deoxyoligonucleotide attached covalently to a polymer support (1-4). Although these phosphoramidites can be prepared by existing methods (5,6) from the appropriately protected deoxynucleosides la-d, the chlorophosphines 2 and 3 used in forming 7a-d and 8a-d, respectively, are difficult to prepare and easily react with trace amounts of water. Moreover, the high reactivity of 2 and 3 and the concomitant production of insoluble amine hydrochloride salts preclude their use for any strategy involving the in situ generation of deoxynucleoside phosphoramidites for deoxyoligonucleotide synthesis on solid supports (7). Because of our interest in the latter approach, we were prompted to investigate the relative stability and reactivity of the aminophosphines 4, 5, and 6 towards phosphodiester formation. We wish to report that the phosphoramidites 7a-d and 8a-d can be prepared in good yields by the reaction of suitably protected deoxynucleosides la-d and bis-dialkylaminophosphines 4 or 6 using amine salts 9 and 10, respectively, as catalysts. This method was applied to a

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An investigation of several deoxynucleoside phosphoramidites useful for synthesizing deoxyoligonucleotides

Cited by 541 publications

References 5 publications

Selective siRNA-mediated suppression of 5-HT1A autoreceptors evokes strong anti-depressant-like effects

Selective siRNA-mediated suppression of 5-HT1A autoreceptors evokes strong anti-depressant-like effects

Anthracycline binding to DNA

In situactivation of bis-dialkylaminophosphines—a new method for synthesizing deoxyoligonucleotides on polymer supports

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