Leupeptin, also known as ''N''-acetyl-
L-leucyl-
L-leucyl-
L-argininal, is a naturally occurring
protease inhibitor that can inhibit cysteine, serine and threonine peptidases.
It is often used during ''in vitro'' experiments when a specific enzymatic reaction is being studied. When cells are lysed for these studies,
proteases, many of which are contained within
lysosomes, are released. These proteases, if freely present in the lysate, would destroy any products from the reaction being studied, and make the experiment uninterpretable. For example, leupeptin could be used in a
calpain extraction to keep calpain from being hydrolyzed by specific proteases. The suggested concentration is 1-10 μM (0.5-5 μg/ml).
Leupeptin is an organic compound produced by
actinomycetes, which inhibits
serine
Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...
,
cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, sometime ...
and
threonine proteases. Leupeptin inhibits serine proteinases (
trypsin (K
i=3.5 nM),
plasmin (K
i= 3.4 nM), porcine
kallikrein), and cysteine proteinases (
papain
Papain, also known as papaya proteinase I, is a cysteine protease () enzyme present in papaya (''Carica papaya'') and mountain papaya (''Vasconcellea cundinamarcensis''). It is the namesake member of the papain-like protease family.
It has wide ...
,
cathepsin B (K
i = 4.1 nM),
endoproteinase Lys-C). It does not inhibit α-
chymotrypsin
Chymotrypsin (, chymotrypsins A and B, alpha-chymar ophth, avazyme, chymar, chymotest, enzeon, quimar, quimotrase, alpha-chymar, alpha-chymotrypsin A, alpha-chymotrypsin) is a digestive enzyme component of pancreatic juice acting in the duodenu ...
or
thrombin. Leupeptin is a competitive transition state inhibitor and its inhibition may be relieved by an excess of substrate.
Leupeptin is soluble in water (stable for 1 week at 4 °C and 1 month at −20 °C), ethanol, acetic acid and DMF.
It can be given topically for middle and inner ear infections.
References
{{Reflist
Protease inhibitors
Tripeptides