SYNTHESIS OF OLIGONUCLEOTIDES CONTAINING 3'-ALKYL CARBOXYLIC-ACIDS USING UNIVERSAL, PHOTOLABILE SOLID-PHASE SYNTHESIS SUPPORTS

The synthesis and application of photolabile supports for solid phase oligonucleotide syntheses that release oligonucleotides containing S'-alkyl carboxylic acids is described. The carboxylic acid functionality is revealed without removing any other protecting groups throughout the biopolymer, and the protected oligonucleotides are amenable to reverse phase HPLC. The solid phase synthesis supports do not contain a nucleoside, making it possible to use a single support for the synthesis of oligonucleotides independent of their sequence. Individual solid phase synthesis supports differ according to the length of the alkyl tether between the 4,4'-dimethoxytrityl group which serves as the initiation site for oligonucleotide synthesis and the latent carboxylic acid. Eicosameric oligonucleotides are obtained in as high as 92% yield, under photolysis conditions that an known to produce less than 1% thymidine thymidine photodimers.