title: Synthesis and SAR study of novel peptide aldehydes as inhibitors of 20S proteasome.
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.
authors: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors: Yuheng
authors: Y
authors: Ma
authors: Bo
authors: B
authors: Xu
authors: Yuan
authors: Y
authors: Fang
authors: Zhenjun
authors: Z
authors: Yang
authors: Jingrong
authors: J
authors: Cui
authors: Liangren
authors: L
authors: Zhang
authors: Lihe
authors: L
authors: Zhang
mesh_terms: D000447:Aldehydes / Q000138:chemical synthesis* / Q000737:chemistry; D020816:Amino Acid Motifs; D001665:Binding Sites; D003198:Computer Simulation; D057075:Enzyme Assays; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry; D061988:Proteasome Inhibitors; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D000447:Aldehydes; D009842:Oligopeptides; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex