Dipartimento di Scienze del Farmaco, Università "G. d'Annunzio", Via dei Vestini, 66013 Chieti, Italy.
ChemMedChem. 2010 Mar 1;5(3):428-35. doi: 10.1002/cmdc.200900393.
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.
S100B 通过结合 p53 的 C 末端并抑制其肿瘤抑制功能来促进细胞增殖。据报道，使用多种计算方法筛选针对人 S100B-p53 相互作用位点的片段文库。这种计算机筛选导致了 280 种新型潜在配体的鉴定。NMR 光谱实验显示，这些化合物中有一组在 p53 相互作用位点具有特异性结合，并证实了它们进一步合理优化的潜力。其中一种结合物的 X 射线晶体结构确定揭示了关键的分子间相互作用，从而为基于结构的配体优化铺平了道路。
