A Universal Glass Support for Oligonucleotide Synthesis

Abstract

A single type of controlled pore glass derivatized with 3-anisoyl-2′(3′)-O-benzoyluridine 5′-O-succinyl residues can be used as the support in solid phase syntheses of either oligoribo- or oligodeoxyribonucleotides.     

Novel Photocleavable Universal Support for Oligonucleotide Synthesis

Abstract

A novel photocleavable universal support for the automated solid phase synthesis of oligonucleotides is described. The linker between the growing oligonucleotide chain and CPG support contains a nucleophilic amine protected with a photocleavable group. On exposure to UV light, this group is detached and the free amine affords cleavage of the oligonucleotide from the support. The use of long wavelength UV light avoids damage to the DNA.     

Stereochemical Problems in Oligonucleotide Synthesis

Abstract

The phosphoramidites of protected cordycepin, thymidine and deoxyadenosine were prepared and the two isomers were well separated by medium-pressure chromatography. Condensations were performed in solution to dimers and on solid support to oligomers. The stereochemical consequences will be discussed.     

Synthesis of Circular Oligonucleotide Conjugates

Abstract

A new approach to the non-template synthesis of circular oligodeoxyribonucleotides containing flexible non-nucleotidic linkers has been developed. Using this technique a set of circular molecules representing triple helix forming, antisense and guanosine tetrad containing oligonucleotides has been obtained.     

Express Protocol for Functionalization of Polymer Supports for Oligonucleotide Synthesis

Abstract

A rapid and general one-pot method is described for the attachment of the leader nucleoside onto the polymer supports, suitable for polymer supported oligonucleotide synthesis following oxidation-reduction condensation. The method can also be used for support functionalisation in fully automated DNA synthesizer prior to oligonucleotide synthesis.     

Versatile Solid Supports for Oligonucleotide Synthesis that Incorporate Urea Bridge

The universal solid support, USIII, representing a new and improved version of commercial USII, as well as 2 ′-deoxynucleoside and 2 ′-deoxy-2 ′-fluoronucleoside bound supports, incorporating a labile phenoxyacetyl fragment, was synthesized by an aminomethyl polystyrene carbamoylation with corresponding azides in the presence of aqueous triethylammonium bicarbonate. All three solid phases incorporate a stable urea tether, thus bridging the polymer and functional linker. These new matrices proved to be potent solid phases for the synthesis of DNA, RNA, or modified oligonucleotides as well as randomized mixed 2 ′-ribo/2 ′-deoxy-2 ′-fluoro-RNA libraries and/or DNA libraries, randomized with trinucleotides (codons).     

Synthesis of an Oligonucleotide Analogue of Ethenoadenosine

Abstract

A phosphoramidite building block derived from 11-carboxy-1,N ⁶-ethenoadenosine has been prepared to be used in a solid supported oligonucleotide synthesis.     

Semi-Mechanized Simultaneous Synthesis of Multiple Oligonucleotide Fragments

Abstract

A new strategy for the simultaneous synthesis of multiple oligonucleotides is described, which is based on asynchronous chain growth and use of a maximum number of support segments in each elongation. An approach to the mechanization of this strategy and applications to the preparation of gene fragments and sequentially variant probes are discussed.     

Synthesis of Oligonucleotide Prodrugs Bearing N-Acetyl Nucleobases

Abstract

N-Acetyl oligonucleotides and their prodrugs were synthesized on photolabile solid support. Tm studies showed a decrease of hydridization for N-acetyl A and G and an increase for N-acetyl C. In cells extract, acetyl groups were hydrolysed.     

化学法合成生物素标记寡核苷酸探针

 生物素可通过氨烷基磷酰胺基团连接到寡核苷酸5'末端,反应在水溶液中进行,核苷酸的侧链基团不用保护。我们以这种化学法合成了生物素标记的寡核苷酸探针,其显色灵敏度达50pg,杂交灵敏度达0.4fmol,并与酶标生物素寡核苷酸探针进行了比较,也对两种不同显色体系作了比较。     

A New Approach to Oligonucleotide Synthesis in Solution

Abstract

A new approach, based on the use of 3′-H-phosphonate building blocks, is described for the synthesis of oligonucleotides and their phosphorothioate analogues in solution.

     

Synthesis and Properties of Some Morpholino Oligonucleotide Analogues

Abstract

The solid phase synthesis of the three types of morpholino analogues of nucleic acids has been accomplished and their hybridization properties were evaluated.     

NMR Study and Improvement of H-Phosphonate Oligonucleotide Synthesis

Abstract

The mechanism of the internucleotide condensation and side-reactions in H-phosphonate approach has been investigated. The modification of this method allowed to minimize side-reactions during the preactivation of the nucleotidic component has been developed.     

Evaluation of Sulfur-Transfer Reagents for Large Scale Synthesis of Oligonucleotide Phosphorothioate Analogues

Abstract

Several sulfur-transfer reagents have been evaluated for large scale synthesis of oligonucleotide phosphorothioate analogues, in which 3-ethoxy-1, 2-dithiazoline-5-one (EDITH, 5) shows potential as an alternative to Beaucage reagent.     

Silica Gel Functionalised with Different Spacers as Solid Support for Oligonucleotide Synthesis

Abstract

The phosphotriester method for synthesis of oligonucleotides has been used for evaluating silica with spacer groups. Three different spacers were synthesized of which a long chain alkylamine, a double glycine and a double y-aminobutyric acid unit. Only the double glycine spacer improved the yields of the first condensations and is now routinely used in our laboratory.     

Synthesis of Monomers Bearing at the 2′‐Position Cyanomethoxycarbonyl Group for Phosphoramidite Oligonucleotide Synthesis

A novel series of phosphoroamidites for the synthesis of 2′‐modified oligonucleotides was designed and synthesized on the base of 2′‐amino uridine and 2′‐amino arabinoadenosine. The amino groups in these compounds were acidified by bis‐cyanomethyl esters of different dicarbonic acids. Generated reactive linker groups containing cyanomethoxycarbonyl groups are stable under conditions of oligonucleotide synthesis but could be easily functionalised in post‐synthetic stage by treatment with compounds bearing primary amino groups.     

Synthesis of 3′-Azido-3′-Deoxythymidine-Terminated Oligonucleotide

Abstract

A method of completely chemical synthesis of 3′-azido-3′-deoxythymidine-terminated oligonucleotides via 5′-H-phosphonate of AZT is described.     

A Rapid Method for the Functionalisation of Polymer Supports for Solid Phase Oligonucleotide Synthesis

Abstract

A rapid method is described for the covalent anchoring of appropriately protected 2′-deoxyribonucleoside-3′-O-succinates to LCAA-CPG, widely used support for solid phase oligonucleotide synthesis. The method involves the reaction of nucleoside-3′-O-succinates with aminoalkyl functions of the support in the presence of improved and commercially available condensing reagent, TBTU or TPP-DTNP to generate fully functionalised polymer supports with excellent nucleoside loadings.     

Synthesis of Biotin-Containing Phosphoramidite Linker with Polyether Spacer Arm

A phosphoramidite linker unit, based on glycerol backbone and containing a biotin residue attached through a tetraethylene glycol spacer arm, was synthesized. DMTr-Glycidol and tetraethylene glycol were used as starting materials. After conversion of one of hydroxy groups in tetraethylene glycol into an amino group, the epoxy cycle in DMTr-glycidol was opened by this amino alcohol, resulting in the corresponding ether and some quantity of secondary amine. After attaching of biotin residue to the ether followed by phosphitylation, the desirable linker was obtained. The structure of the linker was confirmed by ¹H-¹H COSY, ¹H-¹³C HSQC, ¹H-¹³C HMBC, ¹H-¹⁵N HSQC, and ¹H-¹⁵N HMBC spectra. The resulted phosphoramidite linker unit is suitable for use in common DNA synthesizers. This approach can be used for preparation of various modifiers containing reporter groups attached to the primary amino function using conventional procedures.     

Synthesis of New Oligonucleotide Derivatives with Porphyrins and Phthalocyanins

Abstract

The derivatives of oligonucleotides with carboxysubstituted porphyrins and phthalocyanins, Fe(III)hematoporphyrin, Pd(II)coproporphyrin I and Co(II)tetracarboxyphthalocyanin, were synthesized using the common approach.