Synthesis and SAR Study of Novel Peptide Aldehydes as Inhibitors of 20S Proteasome
oleh: Lihe Zhang, Liangren Zhang, Jingrong Cui, Zhenjun Yang, Yuan Fang, Bo Xu, Yuheng Ma
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2011-09-01 |
Deskripsi
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.