Protease Inhibitors from Plants as Therapeutic Agents- A Review

Cid-Gallegos, María Stephanie; Corzo‐Ríos, Luis Jorge; Jiménez‐Martínez, Cristian; Sánchez-Chino, X. M.

doi:10.1007/s11130-022-00949-4

Cited by 43 publications

(28 citation statements)

References 80 publications

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“…In addition to trypsin, KTI binds chymotrypsin, whereas BBTI is reported to associate with chymotrypsin, elastase, cathepsin G, and duodenase . Early calorimetric studies suggested that soybean BBTI binds trypsin 10-100-fold stronger than chymotrypsin .…”

Section: Resultsmentioning

confidence: 99%

“…This limitation can result in pancreatic hypertrophy/hyperplasia, which further impairs the growth of animals . BBTI primarily targets trypsin, chymotrypsin, and elastase, whereas KTI targets aspartic, serine, and cysteine proteases . The mechanism by which TIs inhibit proteases, known as the Laskowski mechanism, consists of slow hydrolysis of the TI in the protease’s active site, with no proteolytic products being released.…”

Section: Introductionmentioning

confidence: 99%

“…6 BBTI primarily targets trypsin, chymotrypsin, and elastase, whereas KTI targets aspartic, serine, and cysteine proteases. 7 The mechanism by which TIs inhibit proteases, known as the Laskowski mechanism, consists of slow hydrolysis of the TI in the protease's active site, with no proteolytic products being released. However, the cleaved TI maintains a similar structure to the intact inhibitor, thus sequestering the protease into a cycle of hydrolysis and resynthesis.…”

Section: Introductionmentioning

confidence: 99%

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Comparative Binding Affinity Analysis of Soybean Meal Bowman-Birk and Kunitz Trypsin Inhibitors in Interactions with Animal Serine Proteases

Okedigba,

Rosso,

et al. 2023

ACS Food Sci. Technol.

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Raw soybeans are not suitable for consumption due to their high levels of anti-nutritional factors, such as trypsin inhibitors (TIs). The two main TIs in soybean, the Kunitz trypsin inhibitor (KTI) and the Bowman-Birk trypsin inhibitor (BBTI), were isolated to evaluate the impact of meal processing on their binding affinities for animal serine proteases. BBTI showed a ∼10fold stronger affinity for trypsin compared to KTI, whereas KTI showed a ∼40-fold stronger affinity for chymotrypsin than BBTI. No correlation was observed between the TI concentration in soybean meal and affinity for trypsin. Further analysis using mass spectrometry and protein sequence identified distinct reactive site loops for protease binding in BBTI and KTI variants, which were associated with their binding affinities for specific serine proteases. Our findings indicate that KTI and BBTI have a preference when interacting with specific animal serine proteases, suggesting that both inhibitors are equally important when considering the nutritional quality of soybean meal, regardless of their concentration.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparative Binding Affinity Analysis of Soybean Meal Bowman-Birk and Kunitz Trypsin Inhibitors in Interactions with Animal Serine Proteases

Okedigba,

Rosso,

et al. 2023

ACS Food Sci. Technol.

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“…Once inactivated, proteins known as antinutritional factors, that is protease inhibitors and lectins, have been reported to show health effects. Protease inhibitors are active towards inflammation and cancer [ 38 ]. Regular consumption of legumes has been shown to reduce the risk of several cancers, such as colon, prostate, gastric, and pancreatic cancer.…”

Section: Nutraceutical Properties Of Legume Proteinsmentioning

confidence: 99%

Legume Proteins and Peptides as Compounds in Nutraceuticals: A Structural Basis for Dietary Health Effects

Carbonaro

Nucara

2022

Nutrients

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In the current climate of food security, quality aspects of legume crops have primary market economic and health impact. Legume proteins and peptides have been discovered to have a role far beyond supplying amino acids for growth and maintenance of body tissues. Several proteins (enzymatic inhibitors, lectins, storage globulins) and peptides derived from them (lunasin, hydrophobic peptides) have shown anticarcinogenic, hypocholesterolemic, glucose-lowering, antioxidant, antimicrobial, and immunostimulant properties. Further understanding of how structural features of legume proteins affect in vivo digestion and production of bioactive sequences represents a key step in the valorization of nutraceutical potentiality of legume proteins and peptides derived from them. In this work, the relationship between structure and bioavailability of protein and peptides are reviewed and discussed.

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“…Marine and plant natural products (NP) provide rich sources of chemically diverse compounds that are biologically active and useful as active therapeutic agents. , Studies have shown that potent and effective protease inhibitors can be identified from NP sources. , For example, gallinamide A is a potent and selective inhibitor of the lysosomal cysteine protease cathepsin L discovered from marine cyanobacteria, which has the potential to reduce SARS-CoV-2 infection . Natural products, both marine and terrestrial, account for ∼50% of small-molecule drugs approved for the treatment of cancer and related conditions; this includes their novel structures as well as their derivatives .…”

Section: Introductionmentioning

confidence: 99%

Discovery of pH-Selective Marine and Plant Natural Product Inhibitors of Cathepsin B Revealed by Screening at Acidic and Neutral pH Conditions

et al. 2022

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Dysregulation of cathepsin B, which involves the translocation of the enzyme from acidic pH lysosomes to the neutral pH cytosol, followed by the initiation of cell death and inflammation, occurs in numerous brain disorders. The wide difference in the acidic pH (4.6) of lysosomes compared to the neutral pH (7.2) of the cytosol suggests that screening at different pH conditions may identify pH-selective modulators of cathepsin B. Therefore, a collection of pure marine and plant natural product (NP) compounds, with synthetic compounds, was screened at pH 4.6 and pH 7.2 in cathepsin B assays, which led to the identification of GER-12 (Crossbyanol B) and GER-24 ((7 Z ,9 Z ,12 Z )-octadeca-7,9,12-trien-5-ynoic acid) marine NP inhibitors at acidic pH but not at neutral pH. GER-12 was effective for the reversible inhibition of cathepsin B, with an IC 50 of 3 μM. GER-24 had an IC 50 of 16 μM and was found to be an irreversible inhibitor. These results show that NP screening at distinct biological pH conditions can lead to the identification of pH-selective cathepsin B modulators. These findings suggest that screening efforts for molecular probes and drug discovery may consider the biological pH environment of the target in the disease process.

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Protease Inhibitors from Plants as Therapeutic Agents- A Review

Cited by 43 publications

References 80 publications

Comparative Binding Affinity Analysis of Soybean Meal Bowman-Birk and Kunitz Trypsin Inhibitors in Interactions with Animal Serine Proteases

Comparative Binding Affinity Analysis of Soybean Meal Bowman-Birk and Kunitz Trypsin Inhibitors in Interactions with Animal Serine Proteases

Legume Proteins and Peptides as Compounds in Nutraceuticals: A Structural Basis for Dietary Health Effects

Discovery of pH-Selective Marine and Plant Natural Product Inhibitors of Cathepsin B Revealed by Screening at Acidic and Neutral pH Conditions

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