Novel Non-Nucleosidic Building Blocks for the Preparation of Multilabeled Oligonucleotides

Abstract

Synthesis of new non-nucleosidic phosphoramidites 1 and 2 derived from achiral precursors containing two reporter groups or amino functions is described. Among them, only phosphoramidites 1a-c allow multiple derivatization of synthetic oligonucleotides. The usefulness of building blocks 1a-c is demonstrated by introduction of several amino functions or fluorescent dansyl reporters at the 3'- and 5'-termini of synthetic oligonucleotides and their phosphorothioate analogues. It is demonstrated that multilabeled non-nucleosidic tether has no or only minor influence on the hybridization properties of the oligonucleotides.

3-Acetyloxy-2-cyano-2-(alkylaminocarbamoyl)propyl Groups as Biodegradable Protecting Groups of Nucleoside 5´-mono-Phosphates

“…2-cyano - N -(2-phenylethyl)acetamide ( 7 ), prepared from ethyl cyanoacetate by acyl substitution with (2-phenylethyl)amine, was bis(hydroxymethylated) by a procedure described earlier [ 37 ]. The 2-cyano-3-hydroxy-2-(hydroxymethyl)- N -(2-phenylethyl)propanamide ( 8 ) thus obtained was then converted to orthoacetate 9 and finally hydrolyzed to 3-acetyloxy-2-cyano-2-hydroxymethyl- N -(2-phenylethyl)propanamide ( 10 ), essentially as described earlier ( Scheme 2 ) [ 38 ]. Alcohol 10 was isolated and used in tetrazole promoted alcoholysis of 3´- O -levulinoylthymidine 5´-( N , N -diethylaminophosphoramidite ( 12 ) [ 29 ] ( Scheme 3 ).…”

Non-nucleosidic analogs of nucleic acids

“…Influence of single nucleotides on the aggregation of oligomers (Nussbaumer et al, 2012) Synthetic non-isotopically labeled oligonucleotides are widely used for sequencing and medical diagnostics, and as probes in molecular biology. Structural modifications of the nucleotide units facilitate the delivery of the nucleic acid into the cells or increase their enzymatic resistance (Guzaev et al, 1996). Langenegger described (Langenegger et al, 2006) synthesis and spectroscopic studies of DNA duplexes that were modified with structurally similar but electronically disparate molecules, e.g.…”

An Aminooxy‐Functionalized Non‐Nucleosidic Phosphoramidite for the Construction of Multiantennary Oligonucleotide Glycoconjugates on a Solid Support

“…Building block S.6 is synthesized from commercially available diethyl 2,2bis(hydroxymethyl)malonate (S.1). It has been shown previously (Guzaev et al, 1996) that S.1 and its mono-4,4 -dimethoxytrityl (DMTr) derivative are decomposed by release of formaldehyde when treated with primary amines. Accordingly, it is necessary to protect both hydroxyl groups of S.1 prior to aminolysis with 3-aminopropanol to obtain S.3.…”