By using the right MS experiments and software tools, antibody proteins can be de novo sequenced routinely. The isobaric Ile and Leu can also be distinguished with w-ions from EThcD spectra.
This case study was adapted, with permission, from McDonald, Z., Chow, S., Gorospe, K., Xu, X., Taylor, P., Liu, Q., Li, Z., Han, Z., Pugh, T., Trudel, S., & Ma., B. (2019). A Large-Scale Comparison of MS-based Antibody De Novo Protein Sequencing and Targeted DNA Sequencing. ASMS 2019 Atlanta, WP 046.