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The amino acid sequence Asp-Glu-Val-Asp (DEVD) corresponds to a sequence within PARP1 [poly(ADP-ribose) polymerase 1], a DNA repair enzyme. The sequence DEVD is cleaved by caspase-3 during cell death by apoptosis.

Derivatives of DEVD such as DEVD-AFC (conjugated to 7-amino-4-trifluoromethyl coumarin) or DEVD-AMC (conjugated to Amino-4-methyl coumarin) are used as fluorometric substrates for enzyme activity assays of caspases (caspase-3) which are detectable following cleavage of the substituted coumarin moiety from the peptide. DEVD-pNA (conjugated to p-nitroanilide) is a colorimetric substrate for caspase enzyme activity assay.

N-Ac-DEVD-N'-MC-R110 is a fluorogenic substrate cleavable in a single step with an enzyme turnover rate and sensitivity for detecting caspase-3 activity in solution and living cells significantly higher than those of other fluorogenic substrates (Wang et al, 2005).

DEVD-CHO (Asp-Glu-Val-Asp-aldehyde) and DEVD-fmk (Asp-Glu-Val-Asp-O-methyl-fluoromethylketone) are synthetic caspase-3 inhibitors.

The N-Acetyl-derivatives of these compounds (Ac-DEVD-AFC, Ac-DEVD-AMC, Ac-DEVD-CHO, Ac-DEVD-fmk) and the N-benzyloxycarbonyl-derivatives (indicated by the prefix z: zDEVD-AFC, zDEVD-fmk) as well as chloromethyl ketone derivatives (cmk; zDEVD-CMK) are also used. Aldehyde conjugates of these tetrapeptides are usually reversible inhibitors. Conjugates with chloromethyl, fluoromethyl, or acyloxymethyl groups usually are irreversible inhibitors.

Treatment of cells with the inhibitory compounds can inhibit characteristic biochemical and morphological events associated with cell death by apoptosis. It should be noted that the peptide derivatives used as inhibitors or substrates can display a wide range of selectivities and potencies against these enzymes. zDEVD-fmk has been shown also to inhibit efficiently cathepsin B activity in vitro and in tissue culture cells at concentrations used to demonstrate the involvement of caspases and thus appears to have non-specific effects.

An enzyme that recognized the DEVD sequence is referred to sometimes also as DEVDase.

For other entries pertaining to cell death mechanisms see also the Apoptosis and Cell Death Dictionary section of this encyclopedia.

Copyright 2012 by H IBELGAUFTS. All rights reserved.


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