Physicochemical property evaluation of modified oligonucleotides by traveling‐wave ion mobility mass spectrometry. (21st March 2022)

• Record Type: Journal Article
• Authors: Omuro, Shogo; Yamaguchi, Takao; Kawase, Taiji; Terasaki, Maki; Hirose, Kenji; Obika, Satoshi
• Is Part Of: Rapid communications in mass spectrometry. Volume 36:Number 10(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-21
• Subjects: Mass spectrometry -- Periodicals; 543.65
• DOI: 10.1002/rcm.9279
• Languages: English
• ISSNs: 0951-4198

Abstract

Abstract : Rationale: Therapeutic oligonucleotides have molecular weights of more than 6000 Da. They typically contain chemically modified structures such as phosphorothioate (PS) and a locked nucleic acid (LNA). To determine the effect of the length and chemical modification on the physicochemical properties, various nucleic acids with different lengths and modified structures were analyzed using traveling‐wave ion mobility mass spectrometry (TWIMS). Methods: The physicochemical characteristics of the modified oligonucleotides were determined using IM‐MS. Each oligonucleotide was evaluated by confirming the multivalent charge state drift times, collision cross‐section (CCS) values, and CCS widths. Results: By plotting the m/z for oligonucleotides of different lengths and the CCS values at each charge state, a bottoming‐out shape plot at one charge per 4.0–3.5 bases was confirmed. Moreover, significant differences were observed in the CCS values between the PS‐modified and unmodified oligonucleotides. The PS‐modified oligonucleotide showed a wider CCS range that was proportional to the PS modification ratio of the oligonucleotide sequence. Conclusions: The TWIMS results showed a correlation between the length and modification of oligonucleotides and the CCS values. In addition, it suggested that each charge state of the oligonucleotide ion has different physicochemical properties.