S100B contributes to cell proliferation by binding the C terminus of p53 and inhibiting its tumor suppressor function. The use of multiple computational approaches to screen fragment libraries targeting the human S100B-p53 interaction site is reported. This in silico screening led to the identification of 280 novel prospective ligands. NMR spectroscopic experiments revealed specific binding at the p53 interaction site for a set of these compounds and confirmed their potential for further rational optimization. The X-ray crystal structure determined for one of the binders revealed key intermolecular interactions, thus paving the way for structure-based ligand optimization.

Fragmenting the S100B–p53 Interaction: CombinedVirtual/Biophysical Screening Approaches to IdentifyLigands / M.Agamennone; L.Cesari; D.Lalli; E.Turlizzi; R. Del Conte; P. Turano; S. Mangani; A. Padova. - In: CHEMMEDCHEM. - ISSN 1860-7179. - STAMPA. - 5:(2010), pp. 428-435. [10.1002/cmdc.200900393]

Fragmenting the S100B–p53 Interaction: CombinedVirtual/Biophysical Screening Approaches to IdentifyLigands

LALLI, DANIELA;DEL CONTE, REBECCA;TURANO, PAOLA;
2010

Abstract

S100B contributes to cell proliferation by binding the C terminus of p53 and inhibiting its tumor suppressor function. The use of multiple computational approaches to screen fragment libraries targeting the human S100B-p53 interaction site is reported. This in silico screening led to the identification of 280 novel prospective ligands. NMR spectroscopic experiments revealed specific binding at the p53 interaction site for a set of these compounds and confirmed their potential for further rational optimization. The X-ray crystal structure determined for one of the binders revealed key intermolecular interactions, thus paving the way for structure-based ligand optimization.
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428
435
M.Agamennone; L.Cesari; D.Lalli; E.Turlizzi; R. Del Conte; P. Turano; S. Mangani; A. Padova
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/373224
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