AEBSF
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{{Refimprove|date=May 2016}}
{{chembox
| Verifiedfields = changed
| verifiedrevid = 477235294
| ImageFile = AEBSF.svg
| ImageClass = skin-invert-image
| ImageSize =
| ImageFile1 = AEBSF-3D-balls.png
| ImageClass1 = bg-transparent
| ImageAlt1 = AEBSF molecule
| PIN = 4-(2-Aminoethyl)benzene-1-sulfonyl fluoride
| OtherNames = Pefabloc SC
| Section1 = {{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 1638
| InChI = 1/C8H10FNO2S/c9-13(11,12)8-3-1-7(2-4-8)5-6-10/h1-4H,5-6,10H2
| InChIKey = MGSKVZWGBWPBTF-UHFFFAOYAK
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1096339
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C8H10FNO2S/c9-13(11,12)8-3-1-7(2-4-8)5-6-10/h1-4H,5-6,10H2
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = MGSKVZWGBWPBTF-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|changed|??}}
| CASNo = 34284-75-8
| CASNo2 = 30827-99-7
| CASNo2_Comment = (hydrochloride salt)
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = F5D36L5354
| PubChem = 1701
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB07347
| SMILES = FS(=O)(=O)c1ccc(cc1)CCN
| MeSHName = AEBSF
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| Section2 = {{Chembox Properties
| Formula = C8H10FNO2S.HCl
| MolarMass = 239.69 g/mol
| Appearance =
| Density =
| MeltingPt =
| BoilingPt =
| Solubility = 200 mg/mL{{cite web |title=Pefabloc® SC |url=https://www.pentapharm.com/wp-content/uploads/2019/05/399-01_DSe_Pefabloc-SC.pdf |publisher=Pentapharm |access-date=22 June 2023}}
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| Section3 = {{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt =
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AEBSF or 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride is a water-soluble, irreversible serine protease inhibitor with a molecular weight of 239.5 Da. It inhibits proteases like chymotrypsin, kallikrein, plasmin, thrombin, and trypsin. The specificity is similar to the inhibitor PMSF, nevertheless AEBSF is more stable at low pH values. Typical usage is 0.1 - 1.0 mM. AEBSF (marketed as Pefabloc SC from the company Pentapharm) was first reported for use in biochemistry in 1993, and came into common use for the inhibition serine proteases and of non-protease enzymes such as acetylhydrolases in the mid 1990s.{{cite journal | last1=Dentan | first1=Christine | last2=Tselepis | first2=Alexandros D. | last3=Chapman | first3=M.John | last4=Ninio | first4=Ewa | title=Pefabloc, 4-[2-aminoethyl]benzenesulfonyl fluoride, is a new, potent nontoxic and irreversible inhibitor of PAF-degrading acetylhydrolase | journal=Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism | publisher=Elsevier BV | volume=1299 | issue=3 | year=1996 | issn=0005-2760 | doi=10.1016/0005-2760(95)00226-x | pages=353–357| pmid=8597590 }}
Mechanism of action
AEBSF is targeted to covalently modify the hydroxyl of serine residues, where it causes an additional 183.0354 Da to be added to each modified residue, but other off-target residues such as tyrosine, lysine, histidine, and the protein N-terminal amino group, have also been reported.{{cite web |title=Web-Based Discussion Forum - Protease Inhibitor Cocktail |url=http://www.abrf.org/index.cfm/list.msg/78308?brSort=auth&expand=all&listName=abrf&urlStr= |publisher=The Association of Biomolecular Resource Facilities (ABRF) |access-date=22 June 2023 |archive-date=3 July 2013 |archive-url=https://archive.today/20130703161237/http://www.abrf.org/index.cfm/list.msg/78308?brSort=auth&expand=all&listName=abrf&urlStr= |url-status=bot: unknown }}{{cite web | title= Accession #: 276 Aminoethylbenzenesulfonylation | website=Unimod | date=2006-10-16 | url=http://www.unimod.org/modifications_view.php?editid1=276 | access-date=2023-06-21}} Due to the substantial frequency of modification of these off-target residues in unoptimized protocols, some users recommend not using AEBSF for highly sensitive proteomics applications, and instead recommend using fresh (and comparatively unstable) PMSF. Both AEBSF and PMSF are sulfonyl fluorides and are sulfonylating agents.{{cite journal | vauthors = Powers JC, Asgian JL, Ekici OD, James KE | title = Irreversible inhibitors of serine, cysteine, and threonine proteases | journal = Chem. Rev. | volume = 102 | issue = 12 | pages = 4735–4736 | year = 2002 | pmid = 12475205 | doi=10.1021/cr010182v}} Sulfonyl fluorides act by reacting with the hydroxy group of the active site serine residue to form a sulfonyl enzyme derivative. This derivative may be stable for long periods of time except at high pH.{{cite journal | vauthors = Gold AM, Fahrney D | title = Sulfonyl Fluorides as Inhibitors of Esterases. II. Formation and Reactions of Phenylmethanesulfonyl α-Chymotrypsin | journal = Biochemistry | volume = 3 | pages = 783–791 | year = 1964 | issue = 6 | pmid = 14211616 | doi=10.1021/bi00894a009}}
Use in cholesterol regulation studies
AEBSF is extensively used in studies aiming to describe cholesterol regulatory genes due to its potent ability to inhibit Site-1-protease (S1P). This serine protease, located in the Golgi apparatus, is responsible for activating the sterol regulatory element-binding proteins (SREBP). By selectively inhibiting S1P, AEBSF can be used to characterize the downstream result of SREBP inhibition and its influence on cholesterol regulation.
See also
References
{{Reflist|2}}
External links
- The MEROPS online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/smi_summary?mid=J00091 AEBSF]
- A Link to the ABRF group usegroup archive with an informative discussion of covalent modifications to proteins resulting from use of AEBSF: [https://archive.today/20130703161237/http://www.abrf.org/index.cfm/list.msg/78308?brSort=auth&expand=all&listName=abrf&urlStr=]
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