Download MendeleyFragmenting the S100B-p53 Interaction: Combined Virtual/Biophysical Screening Approaches to Identify Ligands
Agamennone, M., Cesari, L., Lalli, D., Turlizzi, E., Del Conte, R., Turano, P., Mangani, S., Padova, A.(2010) ChemMedChem 5: 428-435
- PubMed: 20077460
- DOI: https://doi.org/10.1002/cmdc.200900393
- Primary Citation of Related Structures:
3HCM - PubMed 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.
Organizational Affiliation:
Dipartimento di Scienze del Farmaco, Università "G. d'Annunzio", Via dei Vestini, 66013 Chieti, Italy.
