DETAILED CHARACTERIZATION OF ANTISENSE DNA OLIGONUCLEOTIDES

We have developed methods for verification of the structures of novel, chemically synthesized oligonucleotides having alternating methylphos phonate/phosphodiester internucleotide linkages. Matrix-assisted laser desorption ionization mass spectrometry was used to measure the molec ular masses of full-length oligonucleotides, failure synthesis product s, and degradation products formed by enzymatic and chemical means. Th ese measurements provide detailed structural information, including mo lecular mass, length, base composition, complete nucleotide sequence, and confirmation of the sugar moieties and internucleotide linkages.