26305-03-3 Usage
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
Different sources of media describe the Uses of 26305-03-3 differently. You can refer to the following data:
1. Antiviral;Aspartic proteases irreversible inhibitor
2. 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.
3. Pepstatin A are natural, statine-containing peptides that acts as inhibitor of aspartic protease enzymes.
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
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
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
Check Digit Verification of cas no
The CAS Registry Mumber 26305-03-3 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 2,6,3,0 and 5 respectively; the second part has 2 digits, 0 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 26305-03:
(7*2)+(6*6)+(5*3)+(4*0)+(3*5)+(2*0)+(1*3)=83
83 % 10 = 3
So 26305-03-3 is a valid CAS Registry Number.
26305-03-3Relevant articles and documents
Synthesis and biochemical characterisation of fluorinated analogues of pepstatin A and grassystatin A
Lawer, Aggie,Nesvaderani, John,Marcolin, Gabriella M.,Hunter, Luke
, p. 1278 - 1287 (2018)
Pepstatin A and grassystatin A are natural, statine-containing peptides that act as inhibitors of aspartic protease enzymes. In this work, stereoselective fluorination is investigated as a strategy for enhancing the pharmacodynamic and pharmacokinetic properties of these lead compounds. Fluorination is found to modestly affect the protease inhibitory potency, leading to the identification of two highly active new inhibitors of the cancer-associated protease, cathepsin D. However, no dramatic changes are observed in terms of target selectivity, lipophilicity, membrane permeability or metabolic stability.
