Lipofuscin-Like Substances Accumulate Rapidly in Brain, Retina and Internal Organs with Cysteine Protease Inhibition

1990 ◽  
pp. 31-47 ◽  
Author(s):  
G. O. Ivy ◽  
S. Kanai ◽  
M. Ohta ◽  
G. Smith ◽  
Y. Sato ◽  
...  
Keyword(s):  
Cysteine Protease ◽  
Protease Inhibition ◽  
Internal Organs

scholarly journals Mechanistic Insights into the Enhancement of Adeno-Associated Virus Transduction by Proteasome Inhibitors

2013 ◽  
Vol 87 (23) ◽  
pp. 13035-13041 ◽  
Author(s):  
Angela M. Mitchell ◽  
R. Jude Samulski
Keyword(s):  
Cysteine Protease ◽  
Proteasome Inhibitor ◽  
Proteasome Inhibitors ◽  
Proteasome Inhibition ◽  
Proteasome Activity ◽  
Protease Inhibition ◽  
Adeno Associated Virus

Proteasome inhibitors (e.g., bortezomib, MG132) are known to enhance adeno-associated virus (AAV) transduction; however, whether this results from pleotropic proteasome inhibition or off-target serine and/or cysteine protease inhibition remains unresolved. Here, we examined recombinant AAV (rAAV) effects of a new proteasome inhibitor, carfilzomib, which specifically inhibits chymotrypsin-like proteasome activity and no other proteases. We determined that proteasome inhibitors act on rAAV through proteasome inhibition and not serine or cysteine protease inhibition, likely through positive changes late in transduction.

scholarly journals Cysteine protease inhibition prevents mitochondrial apoptosis-inducing factor (AIF) release

2005 ◽  
Vol 12 (11) ◽  
pp. 1445-1448 ◽  
Author(s):  
V J Yuste ◽  
R S Moubarak ◽  
C Delettre ◽  
M Bras ◽  
P Sancho ◽  
...  
Keyword(s):  
Cysteine Protease ◽  
Mitochondrial Apoptosis ◽  
Protease Inhibition ◽  
Apoptosis Inducing Factor

P3-344: Cathepsin B gene deletion and cysteine protease inhibition are effective in a traumatic brain injury model

2012 ◽  
Vol 8 (4S_Part_16) ◽  
pp. P577-P577
Author(s):  
Mark Kindy ◽  
Jin Yu ◽  
Michael Pierschbacher ◽  
Nancy Sipes ◽  
Greg Hook
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cysteine Protease ◽  
Cathepsin B ◽  
Gene Deletion ◽  
Protease Inhibition ◽  
Traumatic Brain Injury Model ◽  
Injury Model

scholarly journals Equilibrium Between Tri- and Tetra-Coordinate Chalcogenuranes Is Critical for Cysteine Protease Inhibition

2020 ◽  
Author(s):  
Gabriela Dias SIlva ◽  
Rodrigo L O R Cunha ◽  
Mauricio Domingues Coutinho Neto
Keyword(s):  
Cysteine Protease ◽  
Density Functional ◽  
Active Form ◽  
Sulfhydryl Group ◽  
Cysteine Proteases ◽  
Inhibition Mechanism ◽  
Direct Reaction ◽  
Exchange Reactions ◽  
Protease Inhibition ◽  
Biological Media

<div>There have been significant advances in the biological use of hypervalent selenium and tellurium compounds as cysteine protease inhibitors over the recent past. However, the full understanding of their reaction mechanisms in aqueous medium and the mechanism of cysteine proteases inhibition is still elusive. Kinetic studies suggest an irreversible inhibition mechanism, which was explained by forming a covalent bond between the enzyme sulfhydryl group and the chalcogen atom at its hypervalent state (+4). However, it is still unclear the active form of the inhibitor present in the aqueous biological media. To uncover this question, we performed a theoretical investigation using density functional theory (DFT). This study investigated chloride ligand exchange reactions by oxygen and sulfur nucleophiles on hypervalent selenium and tellurium compounds. All tetra- and tri-coordinate chalcogen compounds and distinct protonation states of the nucleophiles were considered, totaling 34 unique species, 7</div><div>nucleophiles and 155 free energies rections. We discovered that chloride is easily replaced by a nonprotonated nucleophile (SH<sup>–</sup> or OH<sup>– </sup>) in R<sub>2</sub>SeCl<sub>2</sub> . We also found that</div><div>tri-coordinate species are more stable than their tetra-coordinate counterparts, with selenoxide (R<sub>2</sub>SeO) protonation being strongly exergonic in acid pH. These results suggest that the protonated selenoxide (R<sub>2</sub>SeOH<sup>+</sup>) is the most probable active chemical species in biological media. The computed energetic profiles paint a possible picture for the selenurane activity, with successive exergonic steps leading to a covalent inhibition of thiol dependent enzymes, like cysteine proteases. A second less exergonic pathway has also been uncovered, with a direct reaction to chalcogenonium cation (R<sub>2</sub>SeCl<sup>+</sup>) as the inhibition step. The trends observed for the telluranes were similar, albeit with</div><div>more exergonic reactions and a stronger trend to form bonds with oxygen species then selenuranes.</div><div><br></div>

scholarly journals Using serpins cysteine protease cross-specificity to possibly trap SARS-CoV-2 Mpro with reactive center loop chimera

2020 ◽  
Vol 134 (17) ◽  
pp. 2235-2241
Author(s):  
Mohamad Aman Jairajpuri ◽  
Shoyab Ansari
Keyword(s):  
Cysteine Protease ◽  
Active Site ◽  
Cleavage Site ◽  
Serine Proteases ◽  
Therapeutic Potential ◽  
Cysteine Proteases ◽  
Protease Inhibition ◽  
Reactive Center Loop ◽  
Main Protease ◽  
Reactive Center

Abstract Human serine protease inhibitors (serpins) are the main inhibitors of serine proteases, but some of them also have the capability to effectively inhibit cysteine proteases. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) main protease (Mpro) is a chymotrypsin-type cysteine protease that is needed to produce functional proteins essential for virus replication and transcription. Serpin traps its target proteases by presenting a reactive center loop (RCL) as protease-specific cleavage site, resulting in protease inactivation. Mpro target sites with its active site serine and other flanking residues can possibly interact with serpins. Alternatively, RCL cleavage site of serpins with known evidence of inhibition of cysteine proteases can be replaced by Mpro target site to make chimeric proteins. Purified chimeric serpin can possibly inhibit Mpro that can be assessed indirectly by observing the decrease in ability of Mpro to cleave its chromogenic substrate. Chimeric serpins with best interaction and active site binding and with ability to form 1:1 serpin–Mpro complex in human plasma can be assessed by using SDS/PAGE and Western blot analysis with serpin antibody. Trapping SARS-CoV-2 Mpro cysteine protease using cross-class serpin cysteine protease inhibition activity is a novel idea with significant therapeutic potential.

Quantum mechanics/molecular mechanics studies of the mechanism of cysteine protease inhibition by peptidyl-2,3-epoxyketones

2017 ◽  
Vol 19 (20) ◽  
pp. 12740-12748 ◽  
Author(s):  
Kemel Arafet ◽  
Silvia Ferrer ◽  
Florenci V. González ◽  
Vicent Moliner
Keyword(s):  
Quantum Mechanics ◽  
Life Cycle ◽  
Molecular Mechanics ◽  
Cysteine Protease ◽  
Therapeutic Targets ◽  
Cysteine Proteases ◽  
Protease Inhibition ◽  
Parasitic Protozoa

Cysteine proteases are the most abundant proteases in parasitic protozoa and they are essential enzymes to sustain the life cycle of several of them, thus becoming attractive therapeutic targets for the development of new inhibitors.

Evidence That Serpin Architecture Intrinsically Supports Papain-like Cysteine Protease Inhibition:  Engineering α1-Antitrypsin To Inhibit Cathepsin Proteases†

Biochemistry ◽  
2002 ◽  
Vol 41 (15) ◽  
pp. 4998-5004 ◽  
Author(s):  
James A. Irving ◽  
Robert N. Pike ◽  
Weiwen Dai ◽  
Dieter Brömme ◽  
D. Margaret Worrall ◽  
...  
Keyword(s):  
Cysteine Protease ◽  
Protease Inhibition ◽  
Cathepsin Proteases

Equilibrium between tri‐ and tetra‐coordinate chalcogenuranes is critical for cysteine protease inhibition

2021 ◽  
Author(s):  
Gabriela Dias‐da‐Silva ◽  
Rodrigo Cunha ◽  
Mauricio Coutinho‐Neto
Keyword(s):  
Cysteine Protease ◽  
Protease Inhibition

scholarly journals Experimental study and computational modelling of cruzain cysteine protease inhibition by dipeptidyl nitriles

2018 ◽  
Vol 20 (37) ◽  
pp. 24317-24328 ◽  
Author(s):  
Alberto Monteiro Dos Santos ◽  
Lorenzo Cianni ◽  
Daniela De Vita ◽  
Fabiana Rosini ◽  
Andrei Leitão ◽  
...  
Keyword(s):  
Experimental Study ◽  
Cysteine Protease ◽  
Computational Modelling ◽  
Inhibition Mechanism ◽  
Protease Inhibition ◽  
Reaction Inhibition

A combined computational and experimental study aimed to gain insights into the reaction inhibition mechanism of cruzain by dipeptidyl nitriles.

scholarly journals Cysteine protease inhibition attenuates acute right heart failure

2006 ◽  
Vol 20 (5) ◽  
Author(s):  
HASAN A AHMAD ◽  
Li Lu ◽  
Shuyu Ye ◽  
Ya Xu ◽  
Heather Thompson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cysteine Protease ◽  
Right Heart Failure ◽  
Protease Inhibition ◽  
Right Heart
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