%0 Journal Article
%T Synthesis and SAR Study of Novel Peptide Aldehydes as Inhibitors of 20S Proteasome
%A Yuheng Ma
%A Bo Xu
%A Yuan Fang
%A Zhenjun Yang
%A Jingrong Cui
%A Liangren Zhang
%A Lihe Zhang
%J Molecules
%D 2011
%I MDPI AG
%R 10.3390/molecules16097551
%X 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.
%K 20S proteasome
%K inhibitor
%K peptide aldehydes
%K synthesis
%K structure-activity relationship
%U http://www.mdpi.com/1420-3049/16/9/7551