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Automated solid‐phase synthesis of branched oligonucleotides.

In the past, oligonucleotide synthesis was carried out manuallyusing, as containers for the solid phase, miniature glass columnssimilar in their shape to low-pressure chromatography columns orsyringes equipped with porous filters.Currently, solid-phase oligonucleotide synthesis is carried outautomatically using computer-controlled instruments(oligonucleotide synthesizers) and is technically implemented incolumn, multi-well plate, and array formats. The column format isbest suited for research and large scale applications where ahigh-throughput is not required. Multi-well plate format isdesigned specifically for high-throughput synthesis on small scaleto satisfy the growing demand of industry and academia forsynthetic oligonucleotides. A number of oligonucleotidesynthesizers are available commercially.

Formation of N-branched oligonucleotides as by-products in solid-phase oligonucleotide synthesis

Product Desciption
NittoPhase® solid support utilizes state-of-the-art polymer synthesis capabilities to provide a solid support for therapeutic oligonucleotide synthesis offering the highest available performance at a greatly reduced cost. The superior properties of Nitto’s proprietary formulated cross-linked polystyrene structure deliver increased yields with greater purity at lower unit cost. NittoPhase® thus delivers a positive impact on both the overall cost and quality of both small and large scale oligonucleotide synthesis.


Aziridines in Parallel- and Solid-Phase Synthesis.

The protocols described herein allow for the facile solid‐phase synthesis of branched DNA and/or RNA oligonucleotides of varying chain length, containing symmetrical or asymmetrical sequences immediate to an RNA branch point.

There are two fluorous methods which have now been described to carry this out. One is fluorous tagging as described by Berry and Associates and the other is fluorous capping as described in this patent application. In fluorous tagging, the synthesis is just like regular solid phase synthesis except that the last nucleotide is protected with a fluorous DMT group rather than a normal DMT group. Acetate capping is conducted as usual resulting in a crude mixture containing a bunch of non-fluorous deletion sequences and, hopefully, one fluorous tagged full sequence. The non-fluorous impurities are then readily separated from the fluorous tagged full sequence using FSPE. Gupta and Will do the exact opposite. They use a fluorous capping reagent in place of acetate so that in the end the resulting crude mixture contains a bunch of fluorous deletion sequences along with the desired sequence which is non-fluorous.

Advances in Solid-Phase Cycloadditions for Heterocyclic Synthesis.

Thrity years later, this work inspired, independently, tworesearch groups to adopt the H-phosphonate chemistry to thesolid-phase synthesis using nucleoside H-phosphonate monoesters7 as building blocks and pivaloyl chloride,2,4,6-triisopropylsulfonyl chloride (TPS-Cl), and other compoundsas activators. Thepractical implementation of H-phosphonate method resulted in a veryshort and simple synthetic cycle consisting of only two steps,detritylation and coupling (Scheme 2). ofinternucleosidic H-phosphonate diester 8 tophosphodiester 9 with a solution of in aqueous is carried out atthe end of the chain assembly rather than as a step in thesynthetic cycle. Alternatively, 8 can be convertedto phosphorothioate 9 (X =S).

In the 1970s, substantially more reactive P(III) derivatives ofnucleosides, 3'-O-chlorophosphites, were successfully usedfor the formation of internucleosidic linkages. Thisled to the discovery of the triester methodology. The group ledby M. Caruthers took the advantage of less aggressive and moreselective 1H-terazolidophosphites and implemented themethod on solid phase. Veryshortly after, the workers from the same group further improved themethod by using more stable nucleoside phosphoramidites as buildingblocks. Theuse of 2-cyanoethyl phosphite-protecting group in place of a lessuser-friendly group led to the nucleosidephosphoramidites currently used in oligonucleotide synthesis (seePhosphoramidite building blocks below).Many later improvements to the manufacturing of building blocks,instrumentation, and synthetic protocols made the phosphoramiditechemistry a very reliable and expedite method of choice for thepreparation of synthetic oligonucleotides.

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M., Solid-phase synthesis of C-terminally modified peptides.

In contrast to organic solid-phase synthesis and , the synthesis of oligonucleotides proceeds best onnon-swellable solid supports. The two most often used solid-phasematerials are Controlled Pore (CPG) and macroporous (MPPS).

Solid-phase oligonucleotide synthesis - ATDBio

Since its launch in 2004, NittoPhase® has become the leading solid support in the therapeutic oligonucleotide market, with established results in commercial synthesis up to 600mmol scale.

Solid-Phase Supports for Oligo Synthesis | GEN

To make the solid support material suitable for oligonucleotidesynthesis, non-nucleosidic linkers or nucleoside succinates arecovalently attached to the reactive amino groups in AminopropylCPG, LCAA CPG, or Aminomethyl MPPS. The remaining unreacted aminogroups are capped with . Typically, threeconceptually different groups of solid supports are used.

Solid-phase synthesis of base-sensitive oligonucleotides

After synthesis is complete, the fully protected, solidsupport-bound oligonucleotides are subjected to deprotection usingone of the two general approaches.

Solid phase click ligation for the synthesis of ..

Solid-phase translation and RNA protein fusion:
a novel approach for folding quality control and direct immobilization of proteins using anchored mRNA

Finally the solid-phase synthesis of 5′–5 ..

Preparation, Characterization, and Application of Poly(vinyl alcohol)-graft-Poly(ethylene glycol) Resins: Novel Polymer Matrices for Solid-Phase Synthesis.

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