Synthesis Of Deoxyoligonucleotides Research Articles

Substituted 5-phenyltetrazoles: improved activators of deoxynucleoside phosphoramidites in deoxyoligonucleotide synthesis.

5-(p-nitrophenyl)tetrazole, a tetrazole of enhanced acidity relative to 5-H-tetrazole, is a superior activator of the N-morpholinophosphoramidite in the synthesis of deoxyoligonucleotides.

An investigation of several deoxynucleoside phosphoramidites useful for synthesizing deoxyoligonucleotides

Various deoxynucleoside N,N-dialkylaminomethoxyphosphines were examined for stability and reactivity in deoxyoligonucleotide synthesis. Of those examined, the N-morpholino and N,N-diisopropylamino derivatives most completely satisfied all criteria.

Improvements to solid phase phosphotriester synthesis of deoxyoligonucleotides

A solution of benzenesulphonic acid (3%, w/v) in a dimethylformamide and dichloromethane mixture (9:1, v/v) is shown to be a very effective reagent for the detritylation of deoxyoligonucleotides attached to a solid support. The levels of depurination with this reagent were lower than those observed with other reagents such as trichloroacetic acid. Coupling reactions are described using above ambient temperatures with no detectable increase in side products. Both procedures have been successfully incorporated into an automated system, which can compete with the rate of synthesis by the phosphite approach.

Silica gel: an improved support for the solid-phase phospphotriester synthesis of oligonucleotides

The phosphotriester method for the stepwise synthesis of deoxyoligonucleotides has been employed using HPLC-grade silica gel (Porasil B) as the solid support. The procedure results in a convenient flow-through system for the synthesis of oligomers where all the reaction steps including the zinc bromide method of detritylation are compatible with the selected support. Deoxyoligonucleotides of 25-30 nucleotides in length can be synthesized in high yields utilising stable phosphotriester intermediates. Ease of handling of the solid support allows convenient synthesis of mixed oligonucleotide sequences.

Synthesis of deoxyoligonucleotides on a polymer support

Synthesis of deoxyoligonucleotides on a polymer support

N-acyl protecting groups for deoxynucleosides : A quantitative and comparative study

A detailed study in search for suitable N-acyldeoxy-nucleosides which could serve as building blocks for the stepwise synthesis of deoxyoligonucleotides was undertaken. Several acyl groups namely 4-t-butylphenylacetyl, 4-t-butylphenoxyacetyl, 4-chlorobenzoyl, 3,4-dichlorobenzoyl, 2-methyl-benzoyl, 2,4-dimethylbenzoyl, nicotinoyl, 4-t-butylbenzoyl and 4-phenylazobenzoyl have been used for the protection of the exocyclic amino groups of deoxynucleosides. Interesting data concering the stability of N-acyl groups towards a potent deacylating system (0.2 N NaOH/MeOH) are presented.

The triphenylmethyl (trityl) group and its uses in nucleotide chemistry

The triphenylmethyl (trityl) group can be removed from 5′-trityl 2′-deoxynucleosides (and their N-acyl derivatives) under aprotic neutral conditions without causing any side reactions. An efficient method for tritylation of N-acyl 2′-deoxynucleosides is described. Potential use of such derivatives for stepwise synthesis of deoxyoligonucleotides is discussed.

61] Chemical synthesis of deoxyoligonucleotides by the modified triester method

Publisher Summary This chapter discusses the techniques for the chemical synthesis of deoxyoligonucleotides by the modified triester method. The basic principle of the triester method is to mask each internucleotidic phosphodiester function by a suitable protecting group during the course of the building sequence. As uncharged molecules, the phosphotriester intermediates are soluble in organic solvents and amenable to such conventional purification techniques of organic chemistry as silica-gel column chromatography. After building a desired sequence, all the protecting groups can be removed at the final step to give a deoxyoligonucleotide containing natural 3'→ 5'-phosphodiester bonds. The main advantages of this method are (1) opportunity for large-scale synthesis, (2) short time periods in the purification steps, and (3) high yields using stoichiometric amounts of the reactants. This is due to the absence of any endo-P-O' groups in the oligonucleotide chain thus avoiding chain scission and pyrophosphate formation. As any intermediate oligonucleotide so synthesized always contained a masked 3'-phosphate group, the original necessity of a phosphorylation step at each condensation stage was eliminated, thus simplifying the approach.

Cyanamide mediated syntheses under plausible primitive earth conditions. II. The polymerization of deoxythymidine 5'-triphosphate.

When an aqueous solution (pH 7.0) of 3H deoxythymidine 5'-triphosphate, deoxythymidine 5'-phosphate, 4-amino-5-imidazolecarboxamide, cyanamide and ammonium chloride was dried and heated at 60 degrees C for 18 h, oligomers were obtained in a yield of approximately 80%. After the chemical degradation of any pyrophosphate bonds present in these oligomers, linear polynucleotides of up to 7-8 units in length were isolated by DEAE cellulose column chromatography and identified by enzymatic digestion procedures. The di- and trinucleotide fractions were degraded 87% and 100% by snake venom phosphodiesterase and 39% and 9% by spleen phosphodiesterase. This synthesis of deoxythymidine oligonucleotides was conducted under potentially prebiotic conditions and may offer a possible method for the synthesis of deoxyoligonucleotides on the primitive Earth.

Synthesis of Deoxyoligonucleotides on an Isotactic Polymer Support

Abstract An insoluble and noncross-linked polymer of isotactic polystyrene having a p-methoxytrityl group as part of its structure was chosen as a solid polymer support for deoxyribonucleotide synthesis. The p-methoxytrityl functional group was introduced into the isotactic polymer by benzoylation and Grignard reaction. Judging by the NMR spectra, the isotacticity of the polymer remains unaffected after the modifications. Deoxy-nucleosides were linked to the polymer via 5′ ether group. Condensation of the polymer-nucleoside derivative with 3′ protected nucleotides in the presence of mesitylene sulfonyl chloride resulted in 36-63% coupling to the bound nucleoside. Subsequent condensation gave the trinucleoside diphosphate in 25-57% conversion, based on polymer-bound dinucleoside phosphate. The limitation of the polymer support still lies in the low yield of the coupling step, but the value of an isotactic polymer backbone as a “dendritic” center for chain lengthening remains attractive.

Deoxyoligonucleotide synthesis using a new phosphate protecting group.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDeoxyoligonucleotide synthesis using a new phosphate protecting groupK. L. Agarwal, M. Fridkin, E. Jay, and H. G. KhoranaCite this: J. Am. Chem. Soc. 1973, 95, 6, 2020–2021Publication Date (Print):March 1, 1973Publication History Published online1 May 2002Published inissue 1 March 1973https://doi.org/10.1021/ja00787a055RIGHTS & PERMISSIONSArticle Views83Altmetric-Citations22LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (238 KB) Get e-Alerts Get e-Alerts

Deoxy oligonucleotide synthesis via the triester method.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDeoxy oligonucleotide synthesis via the triester methodJoseph C. Catlin and Friedrich CramerCite this: J. Org. Chem. 1973, 38, 2, 245–250Publication Date (Print):January 1, 1973Publication History Published online1 May 2002Published inissue 1 January 1973https://doi.org/10.1021/jo00942a011RIGHTS & PERMISSIONSArticle Views180Altmetric-Citations81LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (766 KB) Get e-Alerts Get e-Alerts