1) (Figure 1, Page 4), originally introduced in 1997 and known as the McLean support.1 The instability of RNA to strongly basic conditions is caused by the proximity of the 2′-OH group to the phosphodiester group. Attack of the 2′-OH on the adjacent phosphorus gives rise to an energetically favorable 5-membered transition
Universal Support II Fast – cleavage and dephosphorylation in 20 minutes at room temperature Mild – cleavage reagent is 2M ammonia in methanol Compatible with UltraMild, normal, and UltraFast deprotection Cost-effective – comparable in price to regular 2′-deoxynucleoside supports
state, which can open up again to form a mixture of 2′- and 3′-phosphodiester internucleotide linkages, or can lead to chain scission by elimination of the 3′- or 5′-hydroxyl group (Scheme 1, Page 2). In the case of our Universal Support (1), cleavage from the support by hydrolysis of a succinate or, better, the hydroquinone-O,O’-diacetate (Q) linkage, generates a hydroxyl group adjacent to the terminal phosphodiester linkage. Additional base treatment leads to the elimination of the terminal phosphate group and formation of the desired 3’OH (Scheme 2, Page 2). A 3′-Amino-Modifier CPG similar strategy using a neighboring Abasic Site Preparation hydroxyl group to facilitate elimination was Photocleavable Modifiers described by Wengel and Oligo-Peptide Conjugation coworkers.2 A neat variation by Lyttle3 and the Methyl Triester Linkages
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VOLUME 14 NUMBER 1 FEBRUARY 2001
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group at Biosearch Technologies uses a linkage to a polymeric support that is not hydrolyzed by base, so that extended base treatment releases the dephosphorylated oligo, while leaving any undesired byproduct still attached to the support.70-25-7 web The main impediment to the universal adoption of a universal support has been the aggressively basic conditions required to complete the elimination reaction to release the terminal hydroxyl group. The standard reagents used in oligonucleotide deprotection are ammonium hydroxide and aqueous methylamine, which are popular since they are completely volatile. Using these reagents to carry out the elimination reaction requires either high temperature, with attendant high pressure, or extended reaction times. The situation can be improved by adding metal ions to the mix, and Li+, Na+ and Zn2+ have all been used to speed up the elimination reaction, presumably by stabilizing the 5-membered transition state. However, the speed and simplicity of evaporation of the deprotection solution to give the crude oligonucleotide without desalting is not possible with these ionic additives.168273-06-1 MedChemExpress Considerably improved universal supports, using neighboring aminomethyl or diamino-ethyl groups to assist the elimination reaction, were recently described by Azhayev.PMID:30000370 4 Using volatile ammonium hydroxide or aqueous methylamine, terminal dephosphorylation was significantly speeded up and even could be achieved using aqueous zinc chloride. We felt that this setup offered genuine advantages, especially if the oligonucleotides contained base-labile components, but was not quite ideal for mainstream applications. Azhayev’s group then went a step further in the investigation of neighboring group assistance in the dephosphorylation reaction. Amide groups may be considered to be weak N-H acids and can display basic properties in ammonium hydroxide or aqueous methylamine. (-3-Amino-1,2propanediol was acylated to form several amide structures fo.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com