Pepstatin Chemical Properties

Melting point:

233 °C (dec.)(lit.)

alpha 

D27 -90.3° (c = 0.288 in methanol)

Boiling point:

695.91°C (rough estimate)

Density 

1.1340 (rough estimate)

refractive index 

1.7500 (estimate)

storage temp. 

2-8°C

solubility 

10% acetic acid in methanol: 1 mg/mL

form 

White solid

pka

4.17±0.10(Predicted)

color 

Colorless needles

optical activity

Optical rotation: -90.0 ± 5° (c = 0.5, MeOH, 20°C).

Water Solubility 

It is soluble in 10% (v/v) acetic acid in methanol (9:1 methanol:acetic acid) (1 mg/ml), ethanol (1-2 mg/ml with heat up to 60°C), DMSO (5 mg/ml), methanol (1 mg/ml), and acetic acid. Insoluble in benzene, chloroform, water, 1 M NaOH, and ether.

BRN 

2201362

Stability:

Stable. Incompatible with strong bases, strong acids.

InChIKey

JKGWASGTXVCDML-LXTPJMTPSA-N

CAS DataBase Reference

26305-03-3(CAS DataBase Reference)

Safety Information

Safety Statements 

22-24/25

WGK Germany 

2

RTECS 

SC6155000

F 

10

HS Code 

29241990

Toxicity

LD50 in mice, rats, rabbits, dogs (mg/kg): 1090, 875, 820, 450 i.p.; all >2000 orally (Umezawa, 1970)

MSDS

• Language:English Provider:(3S,4S)-3-Hydroxy-4-[[(2S)-2-[[(3S,4S)-3-hydroxy-6-methyl-4-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(3-methylbutanoylamino)butanoyl]amino]butanoyl]amino]heptanoyl]amino]propanoyl]amino]-6-methylheptanoic acid
• Language:English Provider:SigmaAldrich

Pepstatin Usage And Synthesis

Description

Pepstatin A is a bacterial-derived chemotactic pentapeptide that irreversibly inhibits aspartic proteases, including pepsin, gastricsin, renin, cathepsin E, and cathepsin D. Pepstatin A has been reported to stimulate human neutrophil degranulation (EC₅₀ = 0.75 μM) and super oxide production (EC₅₀ = 1.5 μM). Pepstatin A has been widely used as a research tool in studies of protease mechanisms and biological functions and has been examined as a therapeutic agent for inflammatory conditions including gastric ulcer, edema, and hypertension.

Chemical Properties

solid

Uses

Antiviral;Aspartic proteases irreversible inhibitor

Uses

Pepstatin A are natural, statine-containing peptides that acts as inhibitor of aspartic protease enzymes.

Uses

As an aspartic proteases irreversible inhibitor, Pepstain A can be used in conjunction with E64-d and Leupeptin A to inhibit the degradation of autophagic cargo inside autophagosomes.

Definition

ChEBI: Pepstatin A is a pentapeptide isolated from Streptomyces testaceus. It is a potent inhibitor of aspartyl proteases. It has a role as a bacterial metabolite and an EC 3.4.23.* (aspartic endopeptidase) inhibitor. It is a pentapeptide and a secondary carboxamide. It is a conjugate acid of a pepstatin A(1-).

General Description

Pepstatin A is a naturally occurring chemotactic peptide and inhibitor of aspartic proteases that was initially isolated from culture filtrates of various Actinomycetes species, with the initial name simply of “pepstatin”. This name was later modified to “pepstatin A” to distinguish the original pepstatin from later derivatives. Pepstatin A notably contains the unusual amino acid 4-amino-hydroxy-6-methylheptanoic acid (AHMHA), which is known also as statine. The amino acid sequence of pepstatin A is N-Isovaleryl-L-Valyl-L-Valyl-AHMHA-L-Alanyl-AHMHA.

Biochem/physiol Actions

Primary Targetaspartic proteases

Safety Profile

Moderately toxic by intraperitoneal route. When heated to decomposition it emits toxic fumes of NOx.

Enzyme inhibitor

This naturally occurring statine-containing peptidomimetic (FWfree-acid = 685.90 g/mol; CAS 26305-03-3), also called pepstatin A and isovalerylpepstatin and named systematically as N-(isovaleryl)-L-valyl-L-valyl-statylL-alanyl-statine (where the statyl residue is a (3S,4S)-4-amino-3-hydroxy-6- methylheptanoyl residue and the C-terminal statine is the corresponding acid), is a presumptive transition-state analogue for prototypical aspartate proteinase pepsin (Ki = 46 pM). Pepstatin will also inhibit other carboxy proteinases. The inhibitory effectiveness of statine-containing peptides has been widely exploited by incorporating the statine residue into peptides that otherwise match sequence preferences of the target enzyme’s sub-sites. Because pepstatin has a low solubility in water, it is often dissolved indimethyl sulfoxide, methanol, or ethanol. Note that many derivatives of pepstatin are available, each displaying a different spectrum of inhibitory effects. Pepstatin B and C are the N-(n-caproyl)- and N-(iso-caproyl)- derivatives, respectively. Note: Above a critical concentration of 0.1 mM in low ionic-strength and neutral buffers, pepstatin often polymerizes into filaments that be several micrometers in length and have characteristic diameters ranging between 6 and 12 nm

storage

+4°C

References

1) Merck Index 14:7147 2) Marciniszyn?et al.?(1976)?Mode of inhibition of acid proteases by pepstatin; J. Biol. Chem.,?251?7088 3) Oda (2012)?New families of carboxy peptidases: serine-carboxyl peptidases and glutamic peptidases; J. Biochem.,?151?13 4) Yoshida?et al. (2006)?Pepstatin A, an aspartic proteinase inhibitor, suppresses RANKL-induced osteoclast differentiation; J. Biochem.,?139?583

Pepstatin(26305-03-3)Related Product Information

• Kresoxim-methyl
• Basic Violet 1
• Trypsin inhibitor
• CHLOROPHOSPHONAZO III
• Pepsin
• Methyl acrylate
• Methylparaben
• Leupeptin
• Aprotinin
• Methanol
• Acetonitrile
• Paraquat dichloride
• Methyl
• Saccharated Pepsin
• DL-4-Amino-3-hydroxybutyric acid
• (S)-(+)-4-AMINO-3-HYDROXYBUTANOIC ACID
• ACETYL-PEPSTATIN,AC-PEPSTATIN,PEPSTATIN, ACETYL-
• PEPSTATIN A METHYL ESTER