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




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State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China





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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-GluOtBu-Phe-Leucinal 3c, Cbz-GluOtBu-Leu-Leucinal 3d, and Boc-SerOBzl-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





Author: Yuheng Ma, Bo Xu, Yuan Fang, Zhenjun Yang, Jingrong Cui, Liangren Zhang * and Lihe Zhang

Source: http://mdpi.com/



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