Template-Free Segmental Synthesis of Oligonucleotides Containing Nonnative Linkages

• Published in: Journal of organic chemistry Vol. 66; no. 21; pp. 7151 - 7154
• Main Authors: Greenberg, Marc M, Kahl, Jeffrey D
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19.10.2001
• Subjects: Biopolymers - chemistry; Combinatorial Chemistry Techniques - methods; Oligonucleotides - chemical synthesis
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo010610x

Protected oligonucleotides containing 3‘-alkyl carboxylic acids or 3‘-alkylamines were obtained from photolabile solid-phase synthesis supports (1 and 4). Protected oligonucleotides containing 5‘-alkylamines and 3‘-hydroxyl groups were obtained using a photolabile solid-phase synthesis support (2) and a commercially available phosphoramidite reagent (3). Depending upon the source of alkylamine-containing oligonucleotide, the segments were coupled under mild conditions to form products containing either 5‘−3‘ or 3‘−3‘ linkages in good yield and high purity. Oligonucleotides as long as 40 nucleotides were prepared, and coupling yields of protected biopolymer segments were independent of length over the range examined. This method is particularly well suited for the convergent synthesis of oligonucleotides containing nonnative linkages and should be useful for the rapid assembly of modified biopolymers that are useful in biochemical studies.