Small molecules bound to unique sites in the target protein binding cleft of calcium-bound S100B as characterized by nuclear magnetic resonance and x-ray crystallography

X-ray crystallography at 2.10 [Angstrom] (Rfree = 0.257), 1.98 [Angstrom] (Rfree = 0.281), and 1.90 [Angstrom] (Rfree = 0.228) resolution was utilized to determine the structures of three compounds (SBi132, SBi1279, and SBi523) bound to [Ca.sup.2+]-S100B. The findings for SBi132, SBi279, and SBi523 bound to proximal sites on [Ca.sup.2+]-S100B could be applied to design a new class of molecule(s) that interacts with one or more of these binding sites simultaneously, and obtain novel tight binding inhibitors specific for blocking protein-protein interactions involving S100B.