Inhibitory proteináz
Alpha-1-antitrypsin
- Most abundant serine protease inhibitor of human plasma
- Produced in the liver parenchymal cells
- 34 mg/kg/24h is produced
- Normal plasma concentration
- 0,9-1,75 g/l
- Half-life on 3-5 days.
- 5-10 mg alpha-1-antitrypsin inhibit 1.0 mg of trypsin
- Protects tissues from degrading enzymes
- Esp. lungs před neutrophil elastase během infektů
ANTIPAIN
Molecularweight:604.7DaCASnumber:37691--11--5Ki=2×10!!??withserineproteaseassubstrate.Synonym:[(S)--1--Carboxy--2--phenylethyl]carbamoyl--L--arginyl--L--valyl--argininalAntipainisanoligopeptidethathasbeenisolatedfromactinomycetesanditiscommontouseantipainasproteaseinhibitor,specificallyfortrypsinandpapain.Antipainisaserineandcysteinereversibleproteaseinhibitorandbesidestrypsinandpapainitalsoinhibitsasmallamountofplasmintosomeextent.AntipainismostlyusedtoevaluatetheroleofproteasesincelltransformationandtohelpidentifynewproteasesIC50fortrypsinisapproximately0.25µg/mLandasolutionof10mMinwaterorbufferisusuallystableforoneweekat4°Candonemonthat- -20
Aprotinin
- Bovine pancreas trypsin inhibitor (BPTI)
- Competitive substrate analog
- Inactive complex are formed [15]
- protein derived from bovine lung [15]
- 58 AMK
- Three disulfide bonds
- Competitive serine protease inhibitor
- Inhibits
- Chymotrypsin
- Kallikrein
- Plasmin
- Trypsin
- Forms reversible strong complex with enzyme
- Blocks the enzymes active site
- Dissociation at pH <3 or >10
- 1 trypsin inhibitor unit will decrease activity of 2 trypsin units by 50 % [15]
Benzamidine
- Inhibice enteropeptidázy
- Inhibice trypsinu [14]
Beta-site APP-cleaving enzyme1 (BACE1)
- Detected in pancreatic islets
- Inactivate enteropeptidase
- By cleavage of its light chain
- May represent a defense mechanism
- Inhibit enteropeptidase that enters the pancreatic duct accidentally
- Preventing trypsinogen activation in the pancreas [18]
Boronic acid-based pseudopeptides
- Successful and safe drugs for the treatment of various pathologies [16]
- Inhibitory enterokinazy jako metoda k ter. obezity [16]
- Boropeptide compounds [16] derivatives of
- Boroarginine
- Boroornithine
- Borolysine [17]
- Strong, non-absorbable inhibitors of enteropeptidase [17]
- no inhibitory effect on
- Chymotrypsin
- Elastase
- Carboxypeptidase A1
- Carboxypeptidase B1
- Pancreatic lipase
- DPPIV
- Amylase [16]
- Very weak activity against some serine proteases sharing similarities with EP [16]
OBE-2008
- Incorporating a borolysine [16]
- Inhibits both protein and fat absorption
- Undigested intestinal content more solid, less oily stool.
Bortezomid (Velcade®)
- Proteasome inhibitor [16]
FOY-305 (camostat)
- Active synthetic trypsin inhibitors
- Having a guanidinium or amidinium group
- Developed as potential drugs for treatment acute and chronic pancreatitis
- Some of them have been used clinically [14]
Epoxysuccinyl-L-leucylamido (4-guanidino) butane - E-64
- Cysteine proteinase inhibitor [14]
- Inhibice enteropeptidázy
- Inhibice trypsinu [14]
Human serum antitrypsin activity
Velmi chytré, aby při zvýšené střevní propustnosti nedošlo k rychlému vzniku vředů ve střevech a trávení vlastního těla
Význam úrovně antitrypsinové aktivity v těle při akutní pankreatitidě ???
Alfa 1 antitrypsin
- Deficience
- Plicní rozedma !!!
- Vyšší plicní propustnost při infekci
- Razantnější nespecifická fáze plicného zánětu
- Vyšší riziko přechodu do chronicity při infektu Chl. pneumonia
Mají tito jedinci i horší průběh akutní pankreatitidy ?
Profitovali by pacienti s akutní pankreatitidou z infúzí alfa-1-antitrypsinu ap. více než lidé s plicní rozedmou ?
Je po prodělání akutní pankreatitidy vyšší riziko rozvoje plicní rozedmy ?
Inhibitory enteropetidaz
The activity is inhibited by Kunitz pancreatic trypsin inhibitor, BPTI, and small molecule serine protease inhibitors, such as diisopropyl fluorophosphate (DFP), p-aminobenzamidine, and benzamidine, but not by chicken ovomucoid, soybean trypsin inhibitor, chymostatin, pepstatin A, or bestatin.http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/enteropeptidaseLEUPEPTIN
Molecularweight:463,01DaCASnumber:24125--16--4Leupeptin,alsoknownasN--acetyl--L--leucyl--L--leucyl--L--argininal,isasmallpeptidethatiscomposedofthreelinkedaminoacidsandithassomeunusualattributes.Theaminogroupofthecompoundhasanacetylgrouponit;alsoanaldehydegroupreplacestheterminalcarboxygroup.Leupeptinisaproteaseinhibitorthatinhibitstheproteaseswithendopeptidaseactivity(plasmin,trypsin,papain,calpain,andcathepsinB)andthesoilbacteriaStreptomycesproducesitnaturally.Ithasaneffectiveconcentrationof10--100µM(ofcoursedependingontheconcentrationoftheenzyme)anditinhibitstheserineproteasetrypsinwithaKi=3,5nM.Leupeptinissolubleinwater(stableforaboutonemonthat- -20
- -
Lima bean trypsin inhibitor
- Competitive substrate analog
- Inactive complex are formed [15]
- Potent trypsin inhibitor [9]
- Competitive substrate analog
- Inactive complex are formed [15]
- Trypsin inhibitors
- serine protease inhibitor (serpins)
- Largest and most diverse family of protease inhibitors
- Control the activation and catabolism of proteins
- By the inhibition of serine protease in vivo (Lehninger, 2005) [15]
- Competitive substrate analog
- Inactive complex are formed [15]
- Molecular wight 8,000- 24,000 [15]
- Inhibits to a lesser extent also chymotrypsin
- 1mg SBTI inhibits cca 1.0--3.0 mg of trypsin
- Extremely stable
- 1 % sterile filtered solution maintained the activity for over 3 years
- Stored at a temperature at 4-8°C [15]
- SBTI forms 1:1 stoichiometric complex with trypsin [15]
- PH 8.0 is the optimal pH
- As an inhibitor only in native state
- Loss of inhibitory function by denaturation of the soy protein by:
- Heat
- Acid
- Alkali [15]
- Family Zingiberaceae, the Family Pinaceae or the Family Asteraceae. In another embodiment of the invention, the therapeutic compositions comprise at least one plant extract derived from a plant belonging to the Zingiber, Tsuga or Solidago genus of plants. In a further embodiment, the therapeutic composition comprises one or more plant extracts derived from plants selected from the group of: Zingiber officinale, Solidago sp. and Tsuga canadensis. In a further embodiment, the Solidago sp., is Solidago canadensis, Solidago giga?tea (also known as Solidago serotind), Solidago virgaurea, Solidago hybrida, or a combination thereof. In another embodiment of the invention, the therapeutic composition comprises two extracts, where the plant extracts are derived from Zingiber officinale and Solidago sp.
- Simultaneous targeting of two proteases, MMP-9 and cathepsin B. When a composition comprises more than one plant extract, various combinations of MMP-9 and cathepsin B inhibitors are contemplated. For example, the composition may comprise one or more extracts that inhibit MMP-9 only, plus one extract capable of inhibiting cathepsin B and/or MMP-9. Similarly, the composition may comprise one or more extracts that inhibit cathepsin B only, plus one extract capable of inhibiting MMP-9 and/or cathepsin B. Also contemplated is a composition comprising more than one plant extract where each extract is capable of inhibiting both cathepsin B and MMP-9.
- MMP9 je enzym, který hraje roli v růstu a metastázech SCLC. Inhibice MMP9 může pomoci snížit růst a šíření nádoru.
- MMP9 inhibitory mohou být účinné v léčbě SCLC.
- V jedné studii byl u pacientů s pokročilým SCLC, kteří dostávali kombinaci chemoterapie a MMP9 inhibitoru, zaznamenán delší přežití než u pacientů, kteří dostávali pouze chemoterapii.
- Další studie zjistila, že MMP9 inhibitory mohou zlepšit účinnost radioterapie u pacientů s SCLC.
- V současné době probíhá několik klinických studií, které zkoumají účinnost MMP9 inhibitorů v léčbě SCLC.
- This compound is found in berries, nuts, and pomegranates.
- It has been shown to inhibit MMP-9 activity in vitro and in vivo.
- Ellagic acid has also been shown to have anti-inflammatory and antioxidant properties.
- These compounds are found in green tea leaves.
- They have been shown to inhibit MMP-9 activity in vitro and in vivo.
- Green tea catechins have also been shown to have anti-oxidant and anti-inflammatory properties.
- This compound is found in fruits and vegetables, such as apples, onions, and berries.
- It has been shown to inhibit MMP-9 activity in vitro and in vivo.
- Quercetin has also been shown to have anti-inflammatory and antioxidant properties.
- This compound is found in apples, raspberries, and grapes.
- It has been shown to inhibit MMP-9 activity in vitro and in vivo.
- Ursolic acid has also been shown to have anti-inflammatory and antioxidant properties.
- Kyselina ursolová lze zakoupit jako doplněk. Je k dispozici v různých formách, včetně kapslí, tablet a prášku.
- This compound is found in tomatoes, potatoes, and eggplants.
- It has been shown to inhibit MMP-9 activity in vitro and in vivo.
- Solasodine has also been shown to have anti-cancer and anti-inflammatory properties.
- This diverse group of compounds, extracted from pomegranate fruit, exhibits potent MMP-9 inhibitory activity.
- They also possess antioxidant and anti-inflammatory properties, making them promising candidates for the treatment of conditions associated with MMP-9 dysregulation.
- This dietary supplement, rich in catechins, including epigallocatechin gallate (EGCG),
- Has been shown to inhibit MMP-9 activity in vitro and in vivo.
- Its antioxidant and anti-inflammatory properties further contribute to its potential health benefits.
Ovomucoid
List of serine protease inhibitors disclosed in the literature:
Phosphorus-based inhibitors such as the diisopropylphosphofuloridate (DFP) (Jansen et al., (1952) Adv. Enzymol. 13: 321-343) or diphenyl phosphonate ester analogues;
Fluorine-containing serine proteases, such as trifluoromethyl ketones (TFMKs);
Peptide-based aldehydes, chloromethyl ketones, fluoromethyl ketones, dimethyl sulphonium salts, ?-keto-acids and amides, ?-keto esters and ?-keto-aldehydes (glyoxals);
Natural products such as the cyclotheonamides, derived from the Japanese marine sponge Theonella sp.;
Molecules based on heterocyclic structure;
N-hydroxysuccimide heteorcycles and related compounds;
Isocoumarins such as 3,4-dichloroisocoumarin;
ß lactam-based inhibitors;
Metal-potentiated compounds;
Aprotinin (Trasylol®), used to reduce bleeding; and
Serpins (serine protease inhibitors) such as antithrombin and ?-1-antitrypsin having a role in coagulation/thrombosis and emphysema/A1AT respectively.
Serpins
Soybean trypsin inhibitors (SBTI)
Zázvor
Inhibitory MMP9
Ellagic acid:
Green tea catechins:
Quercetin:
Ursolic acid:
Solasodine:
Pomegranate polyphenols:
Green tea extract:
