Small molecule stabilization of diverse amyloidogenic immunoglobulin light chains revealed by hydrogen-deuterium exchange mass spectrometry.

ABSTRACT: Immunoglobulin light chains, a component of antibodies, can misfold and aggregate to cause systemic AL amyloidosis. Aggregation, including amyloid fibril formation, requires unfolding of the full-length light chain from its native state, and in most cases aberrant proteolysis. Small molecules that bind to the native state of light chains to stabilize them against conformational excursions and proteolysis are under development as drug candidates for AL amyloidosis. Since each patient has a unique light chain sequence, a challenge for candidate stabilizer drugs is to bind multiple light chains and suppress their dynamics. Here, we used hydrogen-deuterium exchange measured by mass spectrometry to characterize the binding of six small molecule stabilizers to eleven different λ light chain prot

SUBMITTER: Peterle D 

PROVIDER: S-EPMC12803214 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature