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Molecules 2011, 16(9), 7551-7564; doi:10.3390/molecules16097551
Article

Synthesis and SAR Study of Novel Peptide Aldehydes as Inhibitors of 20S Proteasome

, , , , , *  and
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
* Author to whom correspondence should be addressed.
Received: 1 August 2011 / Revised: 29 August 2011 / Accepted: 30 August 2011 / Published: 5 September 2011
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Abstract

Based on the analysis of the crystal structure of MG101 (1) and 20S proteasomes, a new series of peptide aldehyde derivatives were designed and synthesized. Their ability to inhibit 20S proteasome was assayed. Among them, Cbz-Glu(OtBu)-Phe-Leucinal (3c), Cbz-Glu(OtBu)-Leu-Leucinal (3d), and Boc-Ser(OBzl)-Leu-Leucinal (3o) exhibited the most activity, which represented an order of magnitude enhancement compared with MG132 (2). The covalent docking protocol was used to explore the binding mode. The structure-activity relationship of the peptide aldehyde inhibitors is discussed.
Keywords: 20S proteasome; inhibitor; peptide aldehydes; synthesis; structure-activity relationship 20S proteasome; inhibitor; peptide aldehydes; synthesis; structure-activity relationship
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Ma, Y.; Xu, B.; Fang, Y.; Yang, Z.; Cui, J.; Zhang, L.; Zhang, L. Synthesis and SAR Study of Novel Peptide Aldehydes as Inhibitors of 20S Proteasome. Molecules 2011, 16, 7551-7564.

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