Nostocyclopeptides as New Inhibitors of 20S Proteasome

Abstract

Nostocyclopeptides (Ncps) are a small class of bioactive nonribosomal peptides produced solely by cyanobacteria of the genus Nostoc. In the current work, six Ncps were isolated from Nostoc edaphicum strain CCNP1411. The bioactivity of these compounds was tested in vitro against 20S proteasome, a proteolytic complex that plays an important role in maintaining cellular proteostasis. Dysfunction of the complex leads to many pathological disorders. The assays indicated selective activity of specific Ncp variants. For two linear peptide aldehydes, Ncp-A2-L and Ncp-E2-L, the inhibitory effects on chymotrypsin-like activity were revealed, while the cyclic variant, Ncp-A2, inactivated the trypsin-like site of this enzymatic complex. The aldehyde group was confirmed to be an important element of the chymotrypsin-like activity inhibitors. The nostocyclopeptides, as novel inhibitors of 20S proteasome, increased the number of natural products that can be considered potential regulators of cellular processes.

A comprehensive review of the therapeutic potential of cyanobacterial marine bioactives: Unveiling the hidden treasures of the sea

“…For example, it has been shown that from the cyanobacterium Nostoc sp. isolated cyclic peptide nostocyclopeptide A exhibits antibacterial activity against several Gram‐positive bacteria (Fidor et al, 2021). Similarly, the cyclic peptide microcyclamide 7806A, produced by the cyanobacterium Lyngbya majuscula , has been shown to have potent activity against methicillin‐resistant Staphylococcus aureus (MRSA) (Dahiya et al, 2020).…”