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Study of the prodrugs of peptide aldehydes as proteasome inhibitors

Li-Qiang Han, Yu-An Zhang, Shu-Yang Yao, Bo Xu, Ze-Mei Ge, Jing-Rong Cui, Run-Tao Li*   

  1. State Key Laboratory of Natural and Biomimetic Drugs; Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2011-05-31 Revised:2011-09-10 Online:2012-01-01 Published:2012-01-01
  • Contact: Run-Tao Li*

Abstract: To improve the stability of peptide aldehyde proteasome inhibitors, four peptide cycloacetal derivatives and two peptide heterocycle compounds were designed and synthesized. Their proteasome inhibition and in vitro anticancer activities were evaluated. The four peptide cycloacetal derivatives did not showed any activities, which demonstrated that this kind of cycloacetal derivatives might be suitable as prodrugs. The two peptide heterocycle compounds were found to show obvious activities at both enzyme and cell levels. These results provide us a new clue for the modification of peptide aldehyde proteasome inhibitors.

Key words: Proteasome inhibitor, Anticancer, Peptide acetal derivative, Prodrug principle

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