SYSTEMATIC EXAMINATION OF SUPPORT TYPES IN AUTOMATED SYNTHESES OF LONG OLIGODEOXYRIBONUCLEOTIDES

A nonporous support material consisting of a polytetrafluoroethylene c ore surrounded by a thin layer of polystyrene carrying the anchored nu cleoside is compared with commercial materials in syntheses of long ol igonucleotides. Using standard synthesizer cycles overall yields bette r or comparable to those with commercial wide pore CPG materials were obtained in syntheses of oligonucleotides with target lengths between 100 and 150 nucleotides. Therefore, the concept of chain growth at out er surfaces rather than in pores becomes attractive in efforts to synt hesize long oligonucleotides. Analyses by capillary gel electrophoresi s of syntheses products obtained with CPG1000 as well as with PTFE/PS support materials show that truncated molecules are almost uniformly d istributed in the length interval from 1 up to N-5, Only the portions of missequences near the target lengths are in creased but small compa red to the desired products. Further efforts are necessary to reduce t he amount of this length fractions because their separation from targe ted molecules is extremely difficult.