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Nucleobase derivatives induce in‐source decay of oligonucleotides as new matrix‐assisted laser desorption/ionization matrices
Author(s) -
Kimura Satoshi,
Fujisaka Aki,
Obika Satoshi
Publication year - 2020
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.8620
Subject(s) - nucleobase , oligonucleotide , chemistry , mass spectrometry , matrix assisted laser desorption/ionization , matrix (chemical analysis) , analyte , combinatorial chemistry , dna , desorption , chromatography , organic chemistry , biochemistry , adsorption
Rationale For quality control of oligonucleotide therapeutics, accurate and efficient structural characterization using mass spectrometry techniques, such as liquid chromatography/mass spectrometry (LC/MS) and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS), is essential. In MALDI MS analysis, matrix selection is critical and a new matrix could enable more efficient and rapid structural analysis. Methods We hypothesized that nucleobase derivatives could act as matrices more efficiently than the currently used matrices for oligonucleotides because of structural similarity, which leads to close contact with the analyte. To evaluate their suitability as matrices, 16 nucleobase derivatives were selected and tested as matrix candidates for oligonucleotide analysis. Results Six of the 16 nucleobase derivatives acted as matrices for oligonucleotides. Particularly, 6‐thioguanine (TG) performed well and induced clear in‐source decay fragmentation. When TG or 2‐amino‐6‐chloropurine was used as the matrix, oligonucleotides were ionized, and mainly the w and d fragment ions were observed. Conclusions Herein we demonstrate that a 10‐mer RNA or DNA sequence can be successfully characterized using TG as matrix and suggest the possibility of using nucleobase derivatives as novel matrices in oligonucleotide sequencing.