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

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

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; in revised form: 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

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MDPI and ACS Style

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.

AMA Style

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(9):7551-7564.

Chicago/Turabian Style

Ma, Yuheng; Xu, Bo; Fang, Yuan; Yang, Zhenjun; Cui, Jingrong; Zhang, Liangren; Zhang, Lihe. 2011. "Synthesis and SAR Study of Novel Peptide Aldehydes as Inhibitors of 20S Proteasome." Molecules 16, no. 9: 7551-7564.

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