DEVD sequence

from Wikipedia, the free encyclopedia

With DEVD is in one-letter code , the amino acid sequence from aspartic acid - glutamic acid - valine -aspartic acid (Asp-Glu-Val-Asp), respectively.

The DEVD sequence corresponds to a sequence within the poly-ADP-ribose polymerase 1 (PARP-1), a DNA repair enzyme . The cleavage of the DEVD sequence is catalyzed by caspase-3 during programmed cell death ( apoptosis ). There are a number of different uses of the DEVD sequence in biochemistry.

DEVD derivatives

Various DEVD derivatives, such as DEVD-AMC or DEVD-AFC , are used as fluorometric assays for determining the enzyme activity of the caspases. A fluorescent dye bound to DEVD , for example 7-amino-4-methyl coumarin (AMC), is released by the activity of caspase-3, -6 or -7 and measured by fluorescence spectrometry. The intensity of the fluorescent light correlates directly with the activity of caspases.

With DEVD-CHO (Asp-Glu-Val-Asp-Aldehyde) and DEVD-fmk (Asp-Glu-Val-Asp-O-methyl-fluoromethylketone), two caspase inhibitors have been developed. The N-acetyl variant of DEVD-CHO (AcDEVD-CHO = N-Acetyl-Asp-Glu-Val-Asp-Aldehyde) reduces the neurotoxicity of the chemotherapeutic agents cisplatin , cyclophosphamide , methotrexate , vinblastine and thiotepa .

Individual evidence

  1. ↑ Garcia-Calvo M et al., Purification and catalytic properties of human caspase family members. In: Cell Death & Differentiation , 6/1999, pp. 362-9. PMID 10381624
  2. ↑ Dovi-Akué DAP, Volatile anesthetics induce caspase-dependent apoptosis in Jurkat T lymphocytes (PDF; 1.9 MB), dissertation, Albert-Ludwigs-Universität Freiburg i. Br., 2005
  3. ↑ Rzeski W et al., Excitotoxicity and apoptosis mediate neuronal toxicity of cytostatic agents , in Society for Neuroscience 27th Annual Meeting , Los Angeles 1998
  4. ↑ Rzeski W, Anticancer agents are potent neurotoxins in vitro and in vivo , in Ann Neurol , 56/2004, pp. 351-60. PMID 15349862

literature

  • Schmidt N, Evolution of Programmed Cell Death: Biochemical and Immunohistochemical Studies on Caspases in Hydra , Dissertation, LMU Munich, 2003 (PDF file; 3.64 MB)
  • Fernandes-Alnemri T, Mch3, a novel human apoptotic cysteine ​​protease highly related to CPP32. In: Cancer Research , 55/1995, pp. 6045-52.
  • Fernandes-Alnemri T, In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine ​​protease containing two FADD-like domains. In: Proceedings of the National Academy of Sciences , 93/1996, pp. 7464-9.
  • Garcia-Calvo M et al., Inhibition of human caspases by peptide-based and macromolecular inhibitors. In: Journal of Biological Chemistry , 273/1998, pp. 32608-13.
  • Gurtu V, Fluorometric and colorimetric detection of caspase activity associated with apoptosis. In: Analytical Biochemistry , 251/1997, pp. 98-102.
  • Kidd VJ, Proteolytic activities that mediate apoptosis. In: Annual Review of Physiology , 60/1998, pp. 533-73.
  • Margolin N et al., Substrate and inhibitor specificity of interleukin-1 beta-converting enzyme and related caspases. In: Journal of Biological Chemistry , 272/1997, pp. 7223-8.
  • Muzio M et al., FLICE, a novel FADD-homologous ICE / CED-3-like protease, is recruited to the CD95 (Fas / APO-1) death - inducing signaling complex. In: Cell , 85/1996, pp. 817-27.
  • Nicholson DW et al., Identification and inhibition of the ICE / CED-3 protease necessary for mammalian apoptosis. In: Nature , 376/1995, pp. 37-43.
  • Rotonda J et al., The three-dimensional structure of apopain / CPP32, a key mediator of apoptosis. In: Nature Structural Biology , 3/1996, pp. 619-25.
  • Schotte P et al., Non-specific effects of methyl ketone peptide inhibitors of caspases. In: FEBS Letters , 442/1999, pp. 117-121.
  • Talanian RV et al., Substrate specificities of caspase family proteases. In: Journal of Biological Chemistry , 272/1997, pp. 9677-82.
  • Talanian RV, Allen HJ, Roles of caspases in inflammation and apoptosis: prospects as drug discovery targest. In: Annual Reports in Medicinal Chemistry , 33/1988, pp. 273-82.
  • Thornberry NA et al., A combinatorial approach defines specificities of members of the caspase family and granzyme B. In: Journal of Biological Chemistry , 272/1997, pp. 17907-11.
  • Villa P et al., Caspases and caspase inhibitors. In: Trends in Biochemical Sciences , 22/1997, pp. 388-93.

Web links