Design, synthesis and biological evaluation of dipeptides as novel non-covalent 20S proteasome inhibitors.

Based on the interaction modes of the natural 20S proteasome inhibitors TMC-95A, we have previously discovered a dipeptide 1. To explore the SAR around compound 1, we designed and synthesized a series of dipeptides (8-38) with a fragment-based strategy. Among them, nine compounds showed significant inhibitory activities against the chymotrypsin-like activity of human 20S proteasome with IC50 values at the submicromolar level, which were comparable or even superior to the parent compound 1. Meanwhile, they displayed no significant inhibition against trypsin-like and caspase-like activities of 20S proteasome. The results suggested the feasibility to design dipeptides as novel and potent 20S proteasome inhibitors.[Formula: see text].

Citation

Ya-Jun Yang, Ke Wang, Ying Yang, Fang-Fang Lai, Xiao-Guang Chen, Zhi-Yan Xiao. Design, synthesis and biological evaluation of dipeptides as novel non-covalent 20S proteasome inhibitors. Journal of Asian natural products research. 2021 May;23(5):436-451

Mesh Tags

Substances

PMID: 33844614

search → result