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The proteasome,which controls essential cellular functions such as cell growth,differentiation and apoptosis,has been validated a potential target for cancer therapy.1 Various proteasome inhibitors with different structures and potent anti-cancer activities have been well studied in the last decade.One promising drug bortezomib has been approved by U.S.FDA for the treatment of multiple myeloma and mantle cell lymphoma in 2003 and 2006 respectively.2 The terminal boronic acid of the dipeptide boronate bortezomib,which forms a covalent interaction with the catalytic site of the protein complex,plays a significant role in maintaining its good inhibitory activity against proteasome.3 A series of compounds were designed and synthesized with retained bortezomib dipeptide skeleton and various terminal groups such as hydroxamic acid substituted at the terminal position at the assistance of classical drug design strategies such as bioisosterism.Anti-proliferation experiments in tumor cell models shows moderate anti-tumor activities of target compounds,and the modification is worthy to be further investigated.