NMR reveals site-specific structural signatures of therapeutic antibodies without isotope labeling
Why it matters: Detecting tiny antibody changes without labeling boosts drug safety and speeds biosimilar approval.
- ExCELLS researchers and collaborators combined amino‑acid‑selective labeling, mutagenesis, and multidimensional NMR to assign Fc methyl resonances across alanine, isoleucine, leucine, methionine, threonine, and valine.
- Methyl signals now act as residue‑specific probes that are detectable even at natural isotopic abundance, removing the need for costly labeling.
- Glycosylation patterns—core fucosylation and terminal galactosylation—produce distinct NMR fingerprints, linking structural nuances to antibody effector function.
- Dynamic regions such as the hinge and receptor‑binding interface generate sensitive methyl reporters, revealing local flexibility important for activity.
- Biologic manufacturers can use this label‑free method to monitor structural integrity, streamline biosimilar development, and enhance patient safety.
Researchers at ExCELLS and partners have mapped methyl groups in the Fc region of therapeutic antibodies at residue resolution using NMR—without any isotope labeling. This new approach captures subtle structural variations tied to glycosylation and flexibility, promising tighter quality control and faster biosimilar comparability.
