5’-aminoalkyl oligonucleotides

Recently, Leuck et al. [282] have described an acyl-type anchor for the fast and efficient preparation of 3 -aminoalkyl oligonucleotides based on the 2-hydroxy-methyl-6-nitrobenzoyl group (Figure 19.12). The linker is prepared from 6-nitroph-thalide by acylation of the respective aminoalcohol and attachment to LCAA-CPG through the benzylic hydroxyl via the succinyl group. Cleavage is achieved under conditions of basic hydrolysis by the intramolecular attack of the liberated hydroxyl onto the amide carbonyl with the expulsion of the amine. Complete detachment of the oligomer requires 2 h at 55 °C in concentrated ammonia or 30 min at 65 °C in 40% aqueous methylamine-concentrated aqueous ammonia (l lv/v), or can be accomplished at room temperature within 24 h in concentrated ammonia. The new anchor was shown to be superior to the phthalimido support [279] in terms of product yield and deprotection time. 

However, such modifications are not suited in sequencing and amplification experiments in which the 3 -hydroxy group of the oligonucleotide has to remain free. Both 5-alkylpyrimi-dines and 5 - and 2 -modifications of sugars (2 -alkoxy-, 2 -deoxy-2 -alkylamino- and 2-0-aminoalkyl-linkers) may be applied. 

The hydrolytic stability of branched RNA where the branch-point is a phospho-triester unit revealed that when the triester was embedded within the oligonucleotide it was stable to base-mediated hydrolysis by more than an order of magnitude compared to the simple trinucleotide unit. 5 -Aminoalkyl phosphate nucleotides have been synthesised as analogues of aminoacyl adenylates, and salicyl phospho-diesters of adenylates as potential inhibitors of Mycobacterium tuberculosis. ... 

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