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.

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]

Screening of fibrillogenesis inhibitors of β2-microglobulin : integrated strategies by mass spectrometry capillary electrophoresis and in silico simulations

L. Regazzoni
Primo
;
G. Vistoli;G. Aldini;M. Carini;R. Maffei Facino;
2011

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.
β2-Microglobulin; Affinity screening; Amyloidosis; Capillary electrophoresis; Mass spectrometry; Molecular modeling
Settore CHIM/08 - Chimica Farmaceutica
2011
Article (author)
File in questo prodotto:
File Dimensione Formato  
ANAL CHIM ACTA_2011.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 829.73 kB
Formato Adobe PDF
829.73 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/160695
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 13
social impact