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Background: Animal, epidemiological and clinical studies have demonstrated the anti-tumor activity of pharmacological proteasome inhibitors and the cancer-preventive effects of green tea consumption. Previously, one of our laboratories reported that natural ester bond-containing green tea polyphenols (GTPs), such as (Ϫ)-epigallocatechin-3-gallate [(Ϫ)-EGCG] and (Ϫ)-gallocatechin-3-gallate [(Ϫ)-GCG], are potent and specific proteasome inhibitors. Another of our groups, for the first time, was able to enantioselectively synthesize (Ϫ)-EGCG as well as other analogs of this natural GTP. Our interest in designing and developing novel synthetic GTPs as proteasome inhibitors and potential cancer-preventive agents prompted our current study. Materials and Methods: GTP analogs, (ϩ)-EGCG, (ϩ)-GCG, and a fully benzyl-protected (ϩ)-EGCG [Bn-(ϩ)-EGCG], were prepared by enantioselective synthesis. Inhibition of the proteasome or calpain (as a control) activities under cell-free conditions were measured by fluorogenic substrate assay. Inhibition of intact tumor cell proteasome activity was measured by accumulation of some proteasome target proteins (p27, IB-␣ and Bax) using Western blot analysis.