title: Fragmenting the S100B-p53 interaction: combined virtual/biophysical screening approaches to identify ligands.
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.
authors.affiliation: Dipartimento di Scienze del Farmaco, Università "G. d'Annunzio", Via dei Vestini, 66013 Chieti, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Agamennone
authors.forename: Lucia
authors.initials: L
authors.lastname: Cesari
authors.forename: Daniela
authors.initials: D
authors.lastname: Lalli
authors.forename: Elisa
authors.initials: E
authors.lastname: Turlizzi
authors.forename: Rebecca
authors.initials: R
authors.lastname: Del Conte
authors.forename: Paola
authors.initials: P
authors.lastname: Turano
authors.forename: Stefano
authors.initials: S
authors.lastname: Mangani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padova
mesh_terms: D018360:Crystallography, X-Ray; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D009414:Nerve Growth Factors / Q000737:chemistry / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000737:chemistry / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008024:Ligands; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D016159:Tumor Suppressor Protein p53