Recent highlights in modified oligonucleotide chemistry

Abstract

The synthesis of modified nucleic acids has been the subject of much study ever since the structure of DNA was elucidated by Watson and Crick at Cambridge and Wilkins and Franklin at King's College over half a century ago. This review describes recent developments in the synthesis and application of these artificial nucleic acids, predominantly the phosphoramidites which allow for easy inclusion into oligonucleotides, and is divided into three separate sections. Firstly, modifications to the base portion will be discussed followed secondly by modifications to the sugar portion. Finally, changes in the type of nucleic acid linker will be discussed in the third section. Peptide Nucleic Acids (PNAs) are not discussed in this review as they represent a separate and large area of nucleic acid mimics.

Stereoselective N-Glycosylation of 2-Deoxythioribosides for Fluorescent Nucleoside Synthesis

“…The resulting solution was extracted with CH 2 Cl 2 (2 × 50 mL), and the combined organic layers were dried, filtered, and evaporated in vacuo. The crude material was subjected to column chromatography on silica gel (hexane/EtOAc, 93:7) to give an inseparable isomer mixture of 170.8, 170.3, 137.6, 136.9, 132.7, 132.3, 131.5, 130.5, 129.7, 129.6, 88.1, 86.4, 86.0, 84.4 p-Tolyl-3-O-benzoyl-1-thio-5-O-triisopropylsilyl-2-deoxy-α,β-D-ribofuranoside (6). To a stirring solution of thioglycoside 4 (α/β = 1.0:1.8, 0.405 g, 1.02 mmol) in CH 2 Cl 2 (7.3 mL) were added pyridine (0.80 mL), Et 3 N (0.20 mL, 1.43 mmol), BzCl (0.14 mL, 1.23 mmol), and DMAP (0.012 g, 0.10 mmol).…”

Synthesis and properties of DNA oligonucleotides with a zwitterionic backbone structure

“…Due to the reduced overall negative charge, we anticipate NAA-modified oligonucleotides to possibly display enhanced cellular uptake. Hence, the NAAlinkage might be a useful addition to the 'toolbox' of oligonucleotide modifications 2,3 for the design of therapeutic agents. It should also be noted that the amino group of the NAA-motif might be employed for the selective covalent derivatisation of oligonucleotides with fluorophores or other chemical entities.…”

P-Stereodefined phosphorothioate analogs of glycol nucleic acids—synthesis and structural properties

“…[4][5][6] In phosphorothioate analogs of DNA (PS-DNA) one of the non-bridging phosphate oxygen atoms is replaced with a sulfur atom (Fig. 1A).…”