Screening of fibrillogenesis inhibitors of β2-microglobulin : integrated strategies by mass spectrometry capillary electrophoresis and in silico simulations
Articolo
Data di Pubblicazione:
2011
Citazione:
Screening of fibrillogenesis inhibitors of β2-microglobulin : integrated strategies by mass spectrometry capillary electrophoresis and in silico simulations / L. Regazzoni, R. Colombo, L. Bertoletti, G. Vistoli, G. Aldini, M. Serra, M. Carini, R. Maffei Facino, S. Giorgetti, M. Stoppini, G. Caccialanza, E. De Lorenzi. - In: ANALYTICA CHIMICA ACTA. - ISSN 0003-2670. - 685:2(2011), pp. 153-161. [10.1016/j.aca.2010.11.025]
Abstract:
The challenging search of ligands for the amyloidogenic protein beta(2)-microglobulin led us to set up an integrated strategy that combines analytical techniques and molecular modelling. Using a chemical library composed of 90 sulphonated molecules and a novel MS screening approach, we initially single out a few new binders. To check for anti-amyloid activity, the best hit obtained was thoroughly studied by docking analysis, affinity and refolding experiments by capillary electrophoresis and in vitro fibrillogenesis Thioflavin T test. Correlative analysis of the overall results obtained from the MS screening led to develop an equation able to identify the key factors of the affinity for beta(2)-microglobulin and to predict the affinity for novel derivatives. The proposed equation was then used for a virtual screening of a large compound database. Studies on the new hit thus retrieved confirm the predictive potential of both the equation on affinity and of docking analysis on anti-amyloid activity.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
β2-Microglobulin; Affinity screening; Amyloidosis; Capillary electrophoresis; Mass spectrometry; Molecular modeling
Elenco autori:
L. Regazzoni, R. Colombo, L. Bertoletti, G. Vistoli, G. Aldini, M. Serra, M. Carini, R. Maffei Facino, S. Giorgetti, M. Stoppini, G. Caccialanza, E. De Lorenzi
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