Fiche publication
Date publication
février 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHOULIER Laurence
Tous les auteurs :
Zeder-Lutz G, Choulier L, Besse M, Cousido-Siah A, Figueras FX, Didier B, Jung ML, Podjarny A, Altschuh D
Lien Pubmed
Résumé
We investigated the suitability of surface plasmon resonance (SPR) for providing quantitative binding information from direct screening of a chemical library on protein tyrosine phosphatase 1b (PTP1B). The experimental design was established from simulations to detect binding with K(D) < 10(-)(4) M. The 1120 compounds (cpds) were injected sequentially at concentrations [C(cpd)] of 0.5 or 10 muM over various target surfaces. An optimized evaluation procedure was applied. More than 90% of cpds showed no detectable signal in four screens. The 30 highest responders at C(cpd)=10 muM, of which 25 were selected in at least one of three screens at C(cpd)=0.5 muM, contained 22 promiscuous binders and 8 potential PTP1B-specific binders with K(D) ~10(-)(5) M. Inhibition of PTP1B activity was assayed and confirmed for 6 of these, including sanguinarine, a known PTP1B inhibitor. C(cpd) dependence studies fully confirmed screening conclusions. The quantitative consistency of SPR data led us to propose a structure-activity relationship (SAR) model for developing selective PTP1B inhibitors based on the ranking of 10 arylbutylpiperidine analogs.
Référence
Anal Biochem. 2012 Feb 15;421(2):417-27
