Application of capillary electrophoresis at low pH to oligonucleotides quality control

A method for oligonucleotides analysis by using capillary electrophoresis a t low pH in free solution is described. It may be considered an alternative to classical analytical techniques which use basic buffers and require the presence of sieving media to separate oligonucleotides as a function of th eir length. On the contrary, at low pH oligo nucleotides can be separated o nly depending on their base composition. A large set of samples consisting of 72 synthetic oligonucleotides bearing a 5'-alkylamine moiety and designe d for HLA genotyping were analysed. The quality of these synthetic oligos w as easily assessed, and a single base difference in oligonucleotides of equ al sequence was detected. The results suggest the application of this metho d to the emerging field of mutation detection and single nucleotide polymor fism analysis. (C) 1999 Elsevier Science B.V. All rights reserved.