NJ Bio is proud to share the first published 2D NMR spectra of antibody-drug conjugates (ADCs), showcasing NMR’s ability to deliver deep insights into ADC higher-order structure (HOS) and the structural impacts on efficacy. The HOS can be a great tool for understanding efficacy, toxicity and physiochemical parameters for optimization of ADCs.
In this study, NJ Bio’s NMR and bioconjugation experts used 2D NMR to analyze trastuzumab and its MMAE and DXd conjugates at DAR 2, 4, and 8 to assess how conjugation influences HOS. The NMR analysis revealed that trastuzumab alone produced high-quality spectra across various conditions. Low-DAR conjugates showed spectra highly similar to the native antibody, apart from distinct linker-payload resonances. As DAR increased, many well-dispersed peaks disappeared, and global signal broadening appeared, most prominently in T-MMAE. These spectra demonstrate the promise of biomolecular NMR to provide a direct window into the solution behavior of ADCs.
NJ Bio congratulated the research team—Emily Grasso, Angela Marquard, Zachary Sparta, David Fry, and Naresh Jain on the landmark publication.
The full study is available at: https://www.mdpi.com/1420-3049/30/22/4490