This project entails the experimental validation for newly-designed compstatin variants with predicted inhibitory activities against the activation of the complement system. Compstatin is a 13-residue cyclic peptide that binds to protein C3 and inhibits complement activation. A compstatin analog is currently in Phase I Clinical Trials against age-related macular degeneration, a disease that afflicts a large portion of the aging population. In collaboration with the research group of Professor Christodoulos Floudas of Princeton University, we have used structural and physicochemical analyses and computational methods to design a new set of compstatin variants with predicted higher potencies than previously known variants. We have selected a subset of the new compstatin variants and control variants to perform surface plasmon resonance experiments, which will allow us to experimentally demonstrate binding abilities against purified C3. If the binding results are positive, we will also measure inhibitory activities (IC50’s), using immunological assays and will conduct nuclear magnetic resonance (NMR) experiments for structural analyses. These data will provide the groundwork for further optimization of compstatin variants, using structure-based and physicochemical analysis-based pharmacophore models.