Nostocyclopeptides as new inhibitors of 20s proteasome.

Fidor, Anna; Ceka?a, Katarzyna; Wieczerzak, Ewa; Ceg?owska, Marta; Kasprzykowski, Franciszek; Edwards, Christine; Mazur-Marzec, Hanna

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.

Citation

FIDOR, A., CEKAŁA, K., WIECZERZAK, E., CEGŁOWSKA, M., KASPRZYKOWSKI, F., EDWARDS, C. and MAZUR-MARZEC, H. 2021. Nostocyclopeptides as new inhibitors of 20S proteasome. Biomolecules [online], 11(10), article 1483. Available from: https://doi.org/10.3390/biom11101483

• Journal Article Type: Article
• Acceptance Date: Oct 5, 2021
• Online Publication Date: Oct 8, 2021
• Publication Date: Oct 31, 2021
• Deposit Date: Oct 11, 2021
• Publicly Available Date: Oct 11, 2021
• Journal: Biomolecules
• Electronic ISSN: 2218-273X
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 10
• Article Number: 1483
• DOI: https://doi.org/10.3390/biom11101483
• Keywords: 20S proteasome inhibitors; Cyanobacteria; Nostoc; Nostocyclopeptides
• Public URL: https://rgu-repository.worktribe.com/output/1489527
• Additional Information: The accompanying file contains supplementary figures which can be found at the end of the main text.