Figure 4


Optimal HCD energy and charge density drive proper fragmentation. (A) Relative BNT162b2 Original maximum sequence coverage determined by oligonucleotide mapping as a function of HCD energy. The maximum sequence coverage resulting from each condition is normalized to the final recommended condition (stepped HCD 17, 21, 25). Maximum sequence coverage was restricted only to oligonucleotides identified by BioPharma Finder using a confidence score parameter restriction of 100%. (B) MS/MS spectra and fragment ion coverage of 3 oligonucleotides, presented as a function of HCD energy and oligonucleotide length. The MS/MS spectra are generated using HCD energies: 13, 21, 33, and 45, as applied to 7mer, 14mer, and 21mer oligonucleotides. Fragment ions identified as 5′ (a,b,c,d), 3′ (w,x,y,z), and internal fragments are annotated by color-coding as defined in the key. Identification and annotation of fragment ions was performed using a Visual Basic Excel tool developed in-house. (C) MS/MS spectra and fragment ion coverage of 3 oligonucleotides, presented as a function of oligonucleotide charge and length. MS/MS spectra are generated using a single stepped energy HCD method (17, 21, 25) on low, middle, and high charge states of the same 7mer, 14mer, and 21mer oligonucleotides presented in panel B. Fragment ions identified as 5′ (a,b,c,d), 3′ (w,x,y,z), and internal fragments are annotated by color-coding as defined in the key. Identification and annotation of fragment ions was performed using a Visual Basic Excel tool developed in-house.