Detailed Characterization of Antisense DNA Oligonucleotides

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

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