title: Sulfonated molecules that bind a partially structured species of beta2-microglobulin also influence refolding and fibrillogenesis.
abstract: Human beta2-microglobulin (beta2-m) is a small amyloidogenic protein responsible for dialysis-related amyloidosis, which represents a severe complication of long-term hemodialysis. A therapeutic approach for this amyloidosis could be based on the stabilization of beta2-m through the binding to a small molecule, to possibly inhibit protein misfolding and amyloid fibril formation. The search of a strong ligand of this protein is extremely challenging: by using CE in affinity and refolding experiments we study the effect that previously selected sulfonated molecules have on the equilibrium between the native form and an ensemble of conformers populating the slow phase of beta2-m folding. These data are correlated with the effect that the same molecules exert on in vitro fibrillogenesis experiments.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of Pavia, Pavia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Carazzone
authors.forename: Raffaella
authors.initials: R
authors.lastname: Colombo
authors.forename: Milena
authors.initials: M
authors.lastname: Quaglia
authors.forename: Palma
authors.initials: P
authors.lastname: Mangione
authors.forename: Sara
authors.initials: S
authors.lastname: Raimondi
authors.forename: Sofia
authors.initials: S
authors.lastname: Giorgetti
authors.forename: Gabriele
authors.initials: G
authors.lastname: Caccialanza
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bellotti
authors.forename: Ersilia
authors.initials: E
authors.lastname: De Lorenzi
mesh_terms: D007700:Kinetics; D017510:Protein Folding; D013451:Sulfonic Acids / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D001613:beta 2-Microglobulin / Q000378:metabolism*
chemical_list: D013451:Sulfonic Acids; D001613:beta 2-Microglobulin