26305-03-3

Usage

Uses

Used in Antiviral Applications:
L-Alaninamide, N-(3-methyl-1-oxobutyl)-L-valyl-L-valyl-(3S,4S)-4-amino-3-hydroxy-6-methylheptanoyl-N-[(1S)-1-[(1S)-2-carboxy-1-hydroxyethyl]-3-methylbutyl]is used as an antiviral agent for its ability to inhibit viral replication and protect host cells from viral infection.
Used in Pharmaceutical Industry:
L-Alaninamide, N-(3-methyl-1-oxobutyl)-L-valyl-L-valyl-(3S,4S)-4-amino-3-hydroxy-6-methylheptanoyl-N-[(1S)-1-[(1S)-2-carboxy-1-hydroxyethyl]-3-methylbutyl]is used as an aspartic proteases irreversible inhibitor for its ability to irreversibly bind to and inhibit the activity of aspartic protease enzymes, which play a crucial role in various biological processes and diseases.
Used in Research Applications:
L-Alaninamide, N-(3-methyl-1-oxobutyl)-L-valyl-L-valyl-(3S,4S)-4-amino-3-hydroxy-6-methylheptanoyl-N-[(1S)-1-[(1S)-2-carboxy-1-hydroxyethyl]-3-methylbutyl]is used as a research tool for studying the structure, function, and mechanisms of aspartic proteases and their role in various biological processes and diseases.
Used in Autophagy Regulation:
L-Alaninamide, N-(3-methyl-1-oxobutyl)-L-valyl-L-valyl-(3S,4S)-4-amino-3-hydroxy-6-methylheptanoyl-N-[(1S)-1-[(1S)-2-carboxy-1-hydroxyethyl]-3-methylbutyl]is used in conjunction with other protease inhibitors such as E64-d and Leupeptin A to regulate the degradation of autophagic cargo inside autophagosomes, which is important for understanding the process of autophagy and its role in various cellular functions and diseases.

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

Upstream product

• 503-74-2 3-methylbutyric acid 
• 68858-20-8 Fmoc-Val-OH 
• 35661-39-3 N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine 
• 158257-40-0 (3S,4S)-(9-fluorenylmethoxycarbonyl)-4-amino-3-hydroxy-6-methylheptanoic acid 

Downstream Products

• 161038-08-0 N-(pepstatinyl)propane-1,3-diamine 
• 161038-07-9 N-(t-butyloxycarbonyl)-N'-(pepstatinyl)propane-1,3-diamine 
• 886442-36-0 N-(3-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyloxy)propylcarbonyl)-N'-(pepstatinyl)propane-1,3-diamine 

Relevant academic research and scientific papers

Synthesis and biochemical characterisation of fluorinated analogues of pepstatin A and grassystatin A

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.