Abstract

Desalting oligonucleotides (ONs) for matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) analysis was achieved using a simple dissolve-spin approach. The ON is dissolved in an organic solvent. Insoluble salts are removed by centrifugation. ONs are highly polar molecules and are generally believed insoluble in organic solvents with moderate polarity such as acetonitrile (ACN), 1,4-dioxane, ethyl acetate, and THF. However, we found that in the presence of a suitable proton source such as pyridinium chloride, a quantity of ON that is sufficient for MALDI MS analysis could be dissolved. Because inorganic salts are insoluble in such relatively non-polar solvents, the finding can be utilized for desalting ONs for MALDI MS analysis. Comparisons of MS spectra of intentionally salted ONs that underwent the new desalting procedure with those that did not undergo the procedure provided unambiguous evidence that the desalting method is highly effective.

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