Recent Advances in the Discovery of Novel Peptide Inhibitors Targeting 26S Proteasome

Title:Recent Advances in the Discovery of Novel Peptide Inhibitors Targeting 26S Proteasome

Volume: 18 Issue: 12

Author(s): Xinjie Gu and Shutao Ma*

Affiliation:

• Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan 250012,China

Keywords: 26S proteasome, ubiquitin-proteasome system, peptide inhibitors, design strategy, inhibitory activity, SARs.

Abstract: Background: The 26S proteasome is a proteolytic complex of multimeric protease, which operates at the executive end of the Ubiquitin-Proteasome System (UPS) and degrades the polyubiquitylated proteins.

Methods: After a brief introduction of 26S proteasome and Ubiquitin-Proteasome System (UPS), this review focuses on the structure and function of the 26S proteasome in intracellular protein level regulation. Then, physiological regulation mechanisms and processes are elaborated. In addition, the advantages and defects of approved 26S proteasome inhibitors were discussed. Finally, we summarized the novel peptide 26S proteasome inhibitors according to their structural classifications, highlighting their design strategies, inhibitory activity and Structure-Activity Relationships (SARs).

Results: Cellular function maintenance relies on the proteasome metabolizing intracellular proteins to control intracellular protein levels, which is especially important for cancer cells to survive and proliferate. In primary tumors, proteasomes had a higher level and more potent activity. Currently, the approved small peptide inhibitors have proved their specific 26S proteasome inhibitory effects and considerable antitumor activities, but with obvious defects. Increasingly, novel peptide inhibitors are emerging and possess promising values in cancer therapy.

Conclusion: Overall, the 26S proteasome is an efficient therapeutic target and novel 26S proteasome inhibitors hold potency for cancer therapy.

Cite this article as:

Gu Xinjie and Ma Shutao*, Recent Advances in the Discovery of Novel Peptide Inhibitors Targeting 26S Proteasome, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (12) . https://dx.doi.org/10.2174/1871520618666180813120012