Template-free segmental synthesis of oligonucleotides containing nonnativelinkages

Protected oligonucleotides containing X-alkyl carboxylic acids or X-alkylam ines were obtained from photolabile solid-phase synthesis supports (1 and 4 ). Protected oligonucleotides containing 5'-alkylamines and X-hydroxyl grou ps were obtained using a photolabile solid-phase synthesis support (2) and a commercially available phosphoramidite reagent (3). Depending upon the so urce of alkylamine-containing oligonucleotide, the segments were coupled un der mild conditions to form products containing either 5'-3' or 3'-3' linka ges in good yield and high purity. Oligonucleotides as long as 40 nucleotid es 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 no nnative linkages and should be useful for the rapid assembly of modified bi opolymers that are useful in biochemical studies.