Molecular Interactions of F ullereneDerivativesinHuman S erum and Inflammatory Cells

Fullerenes are a class of nanomaterials with unique electronic properties that can be harnessed for use in various applications. We have found their biologic function critically depends on the structure of the side chain moieties added to the core carbon cage. A therapeutic candidate termed C 70-Tetraglutamate (TGA), previously shown to have potent anti-inflammatory properties, was selected to determine the molecular interactions in human serum and in resting or Fc�µRI -activated human mast cells (MC). The identity of TGA - binding molecules was a nalyzed using NanoLC-MS/MS peptide sequencing technology. We found that TGA predominately bound to alpha -2-macroglobulin precursor, Serpin peptidase inhibitor, and serum albumin in human serum. In non -activated MC, TGA interacted predominantly with aminop eptidase N precursor, dipeptidyl peptidase 4, and human fibroblast activation. In MC activated through Fc�µRI, predominant interactions were observed between TGA and annexin A5, superoxide dismutase, and lysosomal membrane glycoprotein. These studies for t he first time identify serum and cellular substrates of a