| Literature DB >> 29736601 |
Richard Y-C Huang1, Steven R O'Neil2, Daša Lipovšek2, Guodong Chen3.
Abstract
Higher-order structure (HOS) characterization of therapeutic protein-drug conjugates for comprehensive assessment of conjugation-induced protein conformational changes is an important consideration in the biopharmaceutical industry to ensure proper behavior of protein therapeutics. In this study, conformational dynamics of a small therapeutic protein, adnectin 1, together with its drug conjugate were characterized by hydrogen/deuterium exchange mass spectrometry (HDX-MS) with different spatial resolutions. Top-down HDX allows detailed assessment of the residue-level deuterium content in the payload conjugation region. HDX-MS dataset revealed the ability of peptide-based payload/linker to retain deuterium in HDX experiments. Combined results from intact, top-down, and bottom-up HDX indicated no significant conformational changes of adnectin 1 upon payload conjugation. Graphical Abstract ᅟ.Entities:
Keywords: Adnectin; Adnectin-drug conjugate; HDX; Mass spectrometry
Mesh:
Substances:
Year: 2018 PMID: 29736601 DOI: 10.1007/s13361-018-1966-2
Source DB: PubMed Journal: J Am Soc Mass Spectrom ISSN: 1044-0305 Impact factor: 3.109