Title: Design of Inhibitors for S100B
Volume: 5
Issue: 12
Author(s): Joseph Markowitz, Alexander D. MacKerell Jr., France Carrier, Thomas H. Charpentier and David J. Weber
Affiliation:
Keywords:
melanoma, p53 tumor suppressor protein, cyclin-dependent kinase inhibitor, epitope mapping, computer-aided drug design, fluorescence spectroscopy, std-nmr
Abstract: S100B interacts with the p53 protein in a calcium-dependent manner and down-regulates its function as a tumor suppressor. Therefore, inhibiting the S100B-p53 interaction represents a new approach for restoring functional wild-type p53 in cancers with elevated S100B such as found in malignant melanoma. A discussion of the biological rational for targeting S100B and a description of methodologies relevant to the discovery of compounds that inhibit S100B-p53 binding, including computational techniques, structural biology techniques, and cellular assays, is presented.
