Molecules (Sep 2011)

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

  • Lihe Zhang,
  • Liangren Zhang,
  • Jingrong Cui,
  • Zhenjun Yang,
  • Yuan Fang,
  • Bo Xu,
  • Yuheng Ma

DOI
https://doi.org/10.3390/molecules16097551
Journal volume & issue
Vol. 16, no. 9
pp. 7551 – 7564

Abstract

Read online

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.

Keywords