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

Molecules ◽  
2011 ◽  
Vol 16 (9) ◽  
pp. 7551-7564 ◽  
Author(s):  
Yuheng Ma ◽  
Bo Xu ◽  
Yuan Fang ◽  
Zhenjun Yang ◽  
Jingrong Cui ◽  
...  
Keyword(s):  
20S Proteasome ◽  
Peptide Aldehydes ◽  
Sar Study

scholarly journals Synthesis and Evaluation of Macrocyclic Peptide Aldehydes as Potent and Selective Inhibitors of the 20S Proteasome

2016 ◽  
Vol 7 (3) ◽  
pp. 250-255 ◽  
Author(s):  
David L. Wilson ◽  
Isabel Meininger ◽  
Zack Strater ◽  
Stephanie Steiner ◽  
Frederick Tomlin ◽  
...  
Keyword(s):  
20S Proteasome ◽  
Selective Inhibitors ◽  
Peptide Aldehydes ◽  
Macrocyclic Peptide

scholarly journals Nostocyclopeptides as New Inhibitors of 20S Proteasome

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1483
Author(s):  
Anna Fidor ◽  
Katarzyna Cekała ◽  
Ewa Wieczerzak ◽  
Marta Cegłowska ◽  
Franciszek Kasprzykowski ◽  
...  
Keyword(s):  
Aldehyde Group ◽  
20S Proteasome ◽  
Nonribosomal Peptides ◽  
Inhibitory Effects ◽  
Linear Peptide ◽  
Cellular Processes ◽  
Peptide Aldehydes ◽  
Enzymatic Complex ◽  
Selective Activity

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.

Inhibition of human constitutive 20S proteasome and 20S immunoproteasome with novel N ‐terminally modified peptide aldehydes and their antitumor activity

2018 ◽  
Vol 111 (4) ◽  
Author(s):  
Marta Lubos ◽  
Dawid Dębowski ◽  
Ewelina Barcińska ◽  
Annika Meid ◽  
Iwona Inkielewicz‐Stepniak ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
20S Proteasome ◽  
Peptide Aldehydes

Isolation, Synthesis, and SAR Study of Antiplasmodial Anthraquinones from Kniphofia caulescens

Planta Medica ◽  
2013 ◽  
Vol 79 (10) ◽  
Author(s):  
Y Dai ◽  
L Harinantenaina ◽  
PJ Brodie ◽  
JD Bowman ◽  
M Goetz ◽  
...  
Keyword(s):  
Sar Study

SAR study of drimane sesquiterpenes from three Cinnamosma species of Madagascar

Planta Medica ◽  
2014 ◽  
Vol 80 (10) ◽  
Author(s):  
LH Rakotondraibe ◽  
U Muñoz Acuña ◽  
Y Dai ◽  
H Chai ◽  
EJ Carcache de Blanco ◽  
...  
Keyword(s):  
Sar Study

Theoretical Studies of the Acid-Base Equilibria in a Model Active Site of the Human 20S Proteasome

2020 ◽  
Author(s):  
Jon Uranga ◽  
Lukas Hasecke ◽  
Jonny Proppe ◽  
Jan Fingerhut ◽  
Ricardo A. Mata
Keyword(s):  
Active Site ◽  
Boronic Acid ◽  
Computational Study ◽  
Ubiquitin Proteasome System ◽  
Bayesian Optimization ◽  
Inhibition Mechanism ◽  
20S Proteasome ◽  
Acid Base ◽  
Ubiquitin Proteasome ◽  
Infection Cycles

The 20S Proteasome is a macromolecule responsible for the chemical step in the ubiquitin-proteasome system of degrading unnecessary and unused proteins of the cell. It plays a central role both in the rapid growth of cancer cells as well as in viral infection cycles. Herein, we present a computational study of the acid-base equilibria in an active site of the human proteasome, an aspect which is often neglected despite the crucial role protons play in the catalysis. As example substrates, we take the inhibition by epoxy and boronic acid containing warheads. We have combined cluster quantum mechanical calculations, replica exchange molecular dynamics and Bayesian optimization of non-bonded potential terms in the inhibitors. In relation to the latter, we propose an easily scalable approach to the reevaluation of non-bonded potentials making use of QM/MM dynamics information. Our results show that coupled acid-base equilibria need to be considered when modeling the inhibition mechanism. The coupling between a neighboring lysine and the reacting threonine is not affected by the presence of the inhibitor.

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