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

Molecules

Yuheng Ma¹  Bo Xu¹  Yuan Fang¹  Zhenjun Yang¹  Jingrong Cui¹  Liangren Zhang¹ 

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

关键词: 20S proteasome;    inhibitor;    peptide aldehydes;    synthesis;    structure-activity relationship;   

DOI  :  10.3390/molecules16097551

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.