E-64

Names
IUPAC name

(1S,2S)-2-(((S)-1-((4-Guanidinobutyl)amino)-4-methyl-1-oxopentan-2-yl)carbamoyl)cyclopropanecarboxylic acid

Other names

E 64; Proteinase Inhibitor E 64; N-[N-(L-3-trans-carboxyirane-2-carbonyl)-L-leucyl]-agmatine; [1-[N-[(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl]amino]-4-guanidinobutane]

Identifiers

CAS Number

* 66701-25-5 Y

3D model (JSmol)

* Interactive image

Beilstein Reference

| 6666631
ChEBI |

* CHEBI:30270

ChEMBL |

* ChEMBL374508

ChemSpider |

* 110504

DrugBank |

* DB04276

EC Number |

* 613-978-4

KEGG |

* C01341

PubChem CID

* 123985

UNII |

* R76F7856MV

InChI

* InChI=1S/C15H27N5O5/c1-8(2)7-9(20-13(22)10-11(25-10)14(23)24)12(21)18-5-3-4-6-19-15(16)17/h8-11H,3-7H2,1-2H3,(H,18,21)(H,20,22)(H,23,24)(H4,16,17,19)/t9-,10-,11-/m0/s1

Key: LTLYEAJONXGNFG-DCAQKATOSA-N

* InChI=1/C15H27N5O5/c1-8(2)7-9(20-13(22)10-11(25-10)14(23)24)12(21)18-5-3-4-6-19-15(16)17/h8-11H,3-7H2,1-2H3,(H,18,21)(H,20,22)(H,23,24)(H4,16,17,19)/t9-,10-,11-/m0/s1

Key: LTLYEAJONXGNFG-DCAQKATOBY

SMILES

* OC([C@@H]1[C@@H](C(N[C@@H](CC(C)C)C(NCCCCNC(N)=N)=O)=O)O1)=O

Properties

Chemical formula

| C15H27N5O5
Molar mass | 357.411 g·mol−1
Hazards
GHS pictograms |
GHS Signal word | Warning

GHS hazard statements

| H371

GHS precautionary statements

| P260, P264, P270, P309+311, P405, P501

Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Y verify (what is YN ?)
Infobox references

E-64 is an epoxide which can irreversibly inhibit a wide range of cysteine peptidases.

The compound was first isolated and identified from Aspergillus japonicus in 1978.[1] It has since been shown to inhibit many cysteine peptidases such as papain, cathepsin B, cathepsin L, calpain and staphopain.[2]

The low toxic effects of the inhibitor, in addition to its effective mechanism of action, makes E-64 a potential template for drugs to treat diseases where high levels of a cysteine proteases are the primary cause.

## Structure and mechanism of inhibition

E-64 possesses a trans-epoxysuccinic acid group coupled to a modified dipeptide. The covalent attachment of E-64 to the active site cysteine occurs via nucleophillic attack from the thiol group of the cysteine on C2 of the epoxide. Early studies suggested that the amino-4-guanidinobutane bound in the S3' subsite and the leucyl group in the S2' subsite,[3] however published crystal structures of E-64 complexed with papain indicated that E-64 binds via the S subsites.[2]

Mechanism of irreversible inhibition of cysteine peptidases by E-64.

## See also

* Aloxistatin

## References

1. ↑ "Isolation and Characterization of E–64, a New Thiol Protease Inhibitor". Agric. Biol. Chem. 42 (3): 523–528. 1978. doi:10.1080/00021369.1978.10863014.
2. ↑ 2.0 2.1 "Crystal structure of a papain-E-64 complex". Biochemistry 28 (3): 1332–2. 1989. doi:10.1021/bi00429a058. PMID 2713367.
3. ↑ "L-trans-Epoxysuccinyl-leucylamido(4-guanidino)butane (E-64) and its analogues as inhibitors of cysteine proteinases including cathepsins B, H and L.". Biochem. J. 201 (1): 189–98. 1982. doi:10.1042/bj2010189. PMID 7044372.

0.00

(0 votes)

Original source: https://en.wikipedia.org/wiki/E-64. Read more

|

Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:E-64&oldid=2599530"
*[CID]: Compound ID
*[H371]: May cause damage to organs
*[P260]: Do not breathe dust/fume/gas/mist/vapours/spray
*[P264]: Wash … thoroughly after handling
*[P270]: Do not eat, drink or smoke when using this product
*[P309+311]: IF exposed or you feel unwell: Call a POISON CENTER or doctor/physician
*[P405]: Store locked up
*[P501]: Dispose of contents/container to …