Sulfonated molecules that bind a partially structured species of beta2-microglobulin also influence refolding and fibrillogenesis |
| |
Authors: | Carazzone Chiara Colombo Raffaella Quaglia Milena Mangione Palma Raimondi Sara Giorgetti Sofia Caccialanza Gabriele Bellotti Vittorio De Lorenzi Ersilia |
| |
Institution: | Department of Pharmaceutical Chemistry, School of Pharmacy, University of Pavia, Pavia, Italy. |
| |
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. |
| |
Keywords: | β2‐Microglobulin Affinity capillary electrophoresis Amyloidosis Fibrillogenesis Refolding kinetics |
本文献已被 PubMed 等数据库收录! |