scholarly journals Differences in the Inhibitory Specificity Distinguish the Efficacy of Plant Protease Inhibitors on Mouse Fibrosarcoma

Plants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 602
Author(s):  
Sonia Yoo Im ◽  
Camila Ramalho Bonturi ◽  
Adriana Miti Nakahata ◽  
Clóvis Ryuichi Nakaie ◽  
Arnildo Pott ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Protease Inhibitors ◽  
Malignant Tumors ◽  
L929 Cell ◽  
Similar Efficacy ◽  
Dependent Manner ◽  
Reactive Site ◽  
L929 Cells ◽  
Plant Protease ◽  
Metalloprotease Inhibitor

Metastasis, the primary cause of death from malignant tumors, is facilitated by multiple protease-mediated processes. Thus, effort has been invested in the development of protease inhibitors to prevent metastasis. Here, we investigated the effects of protease inhibitors including the recombinant inhibitors rBbKI (serine protease inhibitor) and rBbCI (serine and cysteine inhibitor) derived from native inhibitors identified in Bauhinia bauhinioides seeds, and EcTI (serine and metalloprotease inhibitor) isolated from the seeds of Enterolobium contortisiliquum on the mouse fibrosarcoma model (lineage L929). rBbKI inhibited 80% of cell viability of L929 cells after 48 h, while EcTI showed similar efficacy after 72 h. Both inhibitors acted in a dose and time-dependent manner. Conversely, rBbCI did not significantly affect the viability of L929 cells. Confocal microscopy revealed the binding of rBbKI and EcTI to the L929 cell surface. rBbKI inhibited approximately 63% of L929 adhesion to fibronectin, in contrast with EcTI and rBbCI, which did not significantly interfere with adhesion. None of the inhibitors interfered with the L929 cell cycle phases. The synthetic peptide RPGLPVRFESPL-NH2, based on the BbKI reactive site, inhibited 45% of the cellular viability of L929, becoming a promising protease inhibitor due to its ease of synthesis.

scholarly journals The complex world of plant protease inhibitors: Insights into a Kunitz-type cysteine protease inhibitor of Arabidopsis thaliana

2017 ◽  
Vol 11 (1) ◽  
pp. e1368599 ◽  
Author(s):  
Sachin Rustgi ◽  
Edouard Boex-Fontvieille ◽  
Christiane Reinbothe ◽  
Diter von Wettstein ◽  
Steffen Reinbothe
Keyword(s):  
Arabidopsis Thaliana ◽  
Protease Inhibitor ◽  
Protease Inhibitors ◽  
Cysteine Protease ◽  
Cysteine Protease Inhibitor ◽  
Complex World ◽  
Plant Protease ◽  
Kunitz Type

scholarly journals Purification, characterization, and bioassay of putative protease inhibitors from Hevea brasiliensis latex

2017 ◽  
Vol 84 (2) ◽  
Author(s):  
Riza Arief PUTRANTO ◽  
. SISWANTO ◽  
Agustin Sri MULYATNI ◽  
Asmini BUDIANI ◽  
Radite TISTAMA
Keyword(s):  
Protease Inhibitor ◽  
Protease Inhibitors ◽  
Inhibitory Activity ◽  
Hevea Brasiliensis ◽  
Rubber Tree ◽  
Exchange Chromatography ◽  
Mycelium Growth ◽  
Plant Protease ◽  
Putative Protease

Latex, a milky white liquid, is the main product from rubber tree (Hevea brasiliensis). Latex is the cytoplasm of complex cellular networks named laticifers in which it contains many different components, including important proteins. Various types of enzymes carrying functions associated with plant defense against pathogen and wounding have been detected in latex in which one of these enzymes is protease inhibitor (PI). Plant protease inhibitor has tremendous potential as an antifungal agent which can be developed as biofungicide. In this work, protease inhibitors from B-serum (lutoid) of rubber tree latex were isolated and purified using Ion Exchange Chromatography (IEC) technique. Of the total 70 fractions of proteins extracted from the columns, only 26 fractions showed measurable levels of protein. The concentration of obtained putative protease inhibitors (three fractions of IEC) ranged from 0.007 to 0.022 mL/g B-serum. Inhibitory activity against four protease enzymes (subtilisin A, trypsin, α-chymotrypsin, and papain) showed the characteristics of Hevea putative protease inhibitors from B-serum as serine and/or cysteine protease inhibitors with more than 15% inhibitory activity of target protease. Based on SDS-PAGE visualization, the molecular weight of dominant protein considered as Hevea putative protease inhibitors was 21.5 kDa. In vitro bioassay test of antifungal activity for Hevea putative protease inhibitors showed reduced mycelium growth of Ganoderma boninense, Sclerotium sp., and Rigidosporus lignosus.

scholarly journals A Review on Therapeutic Potential of Protease Inhibitors from Medicinal Plants

2019 ◽  
pp. 1-11
Author(s):  
R. N. N. Gamage ◽  
K. D. K. P. Kumari
Keyword(s):  
Protease Inhibitor ◽  
Protease Inhibitors ◽  
Blood Clotting ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Geographical Location ◽  
Therapeutic Agents ◽  
Human Diseases ◽  
Plant Protease ◽  
Protease Specificity

Most of the currently available therapeutic agents, particularly for cardiovascular disorders and cancers are very expensive and induce some serious side effects. Some of these drugs have also become less effective due to the emergence of antibiotic resistance. There is a necessity and great demand for the development of novel efficacious plant-based agents that are of pharmacologically effective. In this connection, this review focuses on therapeutic potential of plant protease inhibitors. Protease inhibitors are of a particular concern at present due to their potent ability to inhibit protease enzymes that are involved in pathogenesis of various human diseases. In addition to their function as protein-degrading enzymes, protease inhibitors are now well-known for their capability to involve in many biological activities as signaling molecules. Plant protease inhibitors are also engaged in several physiological and pathological processes, such as blood clotting, inflammation, immune regulation, apoptosis and carcinogenesis. Therefore, isolation of plant protease inhibitors and evaluation of their therapeutic capacity against chronic human diseases have become a major research interest. Nevertheless, protease inhibitor content and protease specificity vary significantly even in the same plant species depending on the geographical location and environmental factors. Consequently, it is important to identify potent therapeutic potential of each plant protease inhibitor on human health individually.

Adaptive Mechanisms of Insect Pests Against Plant Protease Inhibitors and Future Prospects Related to Crop Protection: A Review

2015 ◽  
Vol 22 (2) ◽  
pp. 149-163 ◽  
Author(s):  
Maria Macedo ◽  
Caio de Oliveira ◽  
Poliene Costa ◽  
Elaine Castelhano ◽  
Marcio Silva-Filho
Keyword(s):  
Protease Inhibitors ◽  
Insect Pests ◽  
Crop Protection ◽  
Future Prospects ◽  
Adaptive Mechanisms ◽  
Plant Protease

Towards simultaneous quantification of protease inhibitors and inflammatory biomarkers in serum for people living with HIV

2020 ◽  
Vol 12 (14) ◽  
pp. 1882-1888
Author(s):  
Pengyi Wang ◽  
Charles S. Venuto ◽  
Raymond Cha ◽  
Benjamin L. Miller
Keyword(s):  
Protease Inhibitor ◽  
Protease Inhibitors ◽  
Inflammatory Biomarkers ◽  
People Living With Hiv ◽  
Inflammatory Biomarker ◽  
Simultaneous Quantification ◽  
Living With Hiv

Detecting small and big molecules together: simultaneous quantification of protease inhibitor (DRV) and inflammatory biomarker in serum by Arrayed Imaging Reflectometry (AIR).

scholarly journals Computer-aided identification of a series of novel ligands showing high potency as hepatitis C virus NS3/4A protease inhibitors

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Stephen Ejeh ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Stephen E. Abechi
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Binding Energy ◽  
Protease Inhibitor ◽  
Protease Inhibitors ◽  
Antiviral Agents ◽  
High Potency ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Abstract Background Hepatitis C virus (HCV) is a global medical condition that causes several life-threatening chronic diseases in the liver. The conventional interferon-free treatment regimens are currently in use by a blend of direct-acting antiviral agents (DAAs) aiming at the viral NS3 protease. However, major concerns may be the issue of DAA-resistant HCV strains and the limited availability to the DAAs due to their high price. Due to this crisis, the developments of a new molecule with high potency as an NS3/4A protease inhibitor of the hepatitis-C virus remain a high priority for medical research. This study aimed to use in-silico methods to identify high potent molecule as an NS3/4A protease inhibitor and investigating the binding energy of the identified molecule in comparison with approved direct-acting antiviral agents (Telaprevir, Simeprevir, and Voxilaprevir) through molecular docking. Results The model obtained by in-silico method have the following statistical records, coefficient of determination (r2) of 0.7704, cross-validation (q2LOO = 0.6914); external test set (r2(pred) = 0.7049) and Y-randomization assessment (cR2p = 0.7025). The results from the model were used to identify 12 new potential human HCV NS3/4A protease inhibitors, and it was observed that the identified molecule is well-fixed when docked with the receptor and was found to have the lowest binding energy of − 10.7, compared to approved direct-acting antiviral agents (Telaprevir, Simeprevir, and Voxilaprevir) with − 9.5, − 10.0, − 10.5 binding energy, respectively. Conclusion The binding affinity (− 10.7) of the newly identified molecule docked with 3D structures of HCV NS3/4a protease/helicase (PDB ID: 4A92) was found to be better than that of Telaprevir, Simeprevir, and Voxilaprevir (approved direct-acting antiviral agents) which are − 9.5, − 10.0, and − 10.5, respectively. Hence, a novel molecule was identified showing high potency as HCV NS3/4a protease inhibitors.

Role of proteolysis in apoptosis: involvement of serine proteases in internucleosomal DNA fragmentation in immature thymocytes

1993 ◽  
Vol 71 (9-10) ◽  
pp. 488-500 ◽  
Author(s):  
Valerie M. Weaver ◽  
Boleslaw Lach ◽  
P. Roy Walker ◽  
Marianna Sikorska
Keyword(s):  
Molecular Weight ◽  
Serine Protease ◽  
High Molecular Weight ◽  
Protease Inhibitors ◽  
Dna Fragmentation ◽  
Dna Cleavage ◽  
Apoptotic Cell ◽  
Dependent Manner ◽  
Serine Protease Inhibitors ◽  
High Molecular Weight Dna

Three chemically distinct serine, but not cysteine, protease inhibitors (phenylmethylsulphonyl fluoride, N-tosyl-L-phenylalanylchloromethyl ketone and 3,4-dichloroisocoumarin) prevented, in a dose-dependent manner, the characteristic apoptotic internucleosomal DNA cleavage (DNA ladder) typically observed in thymocytes in response to dexamethasone and teniposide VM-26. This effect was not the result of a direct inhibition of the Ca2+, Mg2+-dependent endonuclease, since oligonucleosomal DNA cleavage occurred in the presence of these inhibitors in isolated nuclei. The proteolytic step occurred at a very early stage of apoptosis, and preincubation of thymocytes with the inhibitors before dexamethasone or teniposide VM-26 were added irreversibly suppressed ladder formation. This implied that the cellular effector(s) of these compounds preexisted and were not resynthesized in response to the inducers of apoptosis. Serine protease inhibitors also suppressed apoptotic cell shrinkage and complete nuclear collapse, suggesting that these morphological changes were directly related to internucleosomal fragmentation of DNA. However, the serine protease inhibitors did not prevent high molecular weight DNA cleavage (> 50 kilobases) that preceded the ladder formation and thymocytes still died by apoptosis. This supported the view that internucleosomal DNA cleavage, considered to be the biochemical marker of apoptosis, might in fact be a late and dispensable step and that the newly described high molecular weight DNA cleavage might be a better indicator of apoptosis.Key words: serine protease, apoptosis, internucleosomal DNA fragmentation, high molecular weight DNA cleavage, protease inhibitors.

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