Disintegrins
Disintegrins are polypeptides that were first isolated from the venom of various vipers (Viperidae). The sequence is also found as a disintegrin domain in a number of human enzymes, the ADAM metalloproteases . To date, over 25 different disintegrins have been isolated from snake venom.
construction
Disintegrins are water-soluble, cysteine - rich, non- enzymatic peptides that consist of 41 to 84 amino acids in snake venom . In the ADAM proteases, the sequence of the disintegrin domain usually consists of around 90 amino acids. Almost all disintegrins and disintegrin domains, such as also ADAM15 that contain the RGD sequence (Arg-Gly-Asp), for example, to α v β 3 - integrin binds. Other ADAM disintegrins can bind to other integrins. ADAM28 binds to α 4 β 1
In snake venom, the disintegrins cause reduced blood coagulation through binding to the fibrinogen binding receptor - the integrin α IIb β 3 - of the platelets .
The RGD sequence, or as in the case of Obtustatin, the KTS sequence, is presented to the respective receptor at the end of a loop structure of the peptide.
application
The highly specific binding to different receptors make the disintegrins potential active ingredients for the treatment of a number of diseases. The anticoagulant effect can be used, for example, to prevent thrombi . Disintegrins are being tested worldwide for the treatment of cancer , asthma and osteopenia .
The high affinity for certain integrins, which are important for the formation of new blood vessels ( angiogenesis ) during tumor growth (for example α v β 3 ), is of particular interest.
Examples
Selection of some snake disintegrins.
Surname | n amino acids | n cysteine | species |
Albolabrin | 73 | 12 | White-lipped pit viper ( Trimeresurus albolabris ) |
Rhodostomine | 68 | 12 | Malay moccasin viper ( Calloselasma rhodostoma ) |
Trigramine | 72 | 12 | Green pit viper ( Trimeresurus gramineus ) |
Batroxostatin | 71 | 12 | Common Lance Viper ( Bothrops atrox ) |
Elegant | 73 | 12 | Trimeresurus elegans |
Applagin | 71 | 12 | Water moccasin otter ( Agkistrodon piscivorus ) |
Barbourin | 73 | 12 | Little Rattlesnake ( Sistrurus m. Barbouri ) |
Bitistatin | 83 | 14th | Puff adder ( Bitis arietans ) |
Obtustatin | 41 | 8th | Levant Otter ( Macroektivena lebetina ) |
Echistatin | 49 | 8th | Common sand otter ( Echis carinatus ) |
Eristostatin | 49 | 8th | MacMahon viper ( Eristicophis macmahoni ) |
Halysin | 71 | 12 | Halysotter ( Gloydius halys ) |
Kistrin | 68 | 12 | Malay moccasin viper ( Calloselasma rhodostoma ) |
Mambin | 59 | 8th | Jameson's Mamba ( Dendroaspis jamesoni ) |
Tergeminin | 73 | 12 | Western Massassauga ( Sistrurus catenatus tergeminus ) |
Triflavine | 70 | 12 | Habu snake ( Trimeresurus flavoviridis ) |
Individual evidence
- ^ DF Seals and SA Courtneidge: The ADAMs family of metalloproteases: multidomain proteins with multiple functions. In: Genes Dev 17, 2003, pp. 7-30. PMID 12514095 (Review)
- ↑ LC Bridges et al: The lymphocyte metalloprotease MDC-L (ADAM 28) is a ligand for the integrin α 4 β 1 . In: J Biol Chem 277, 2002, pp. 3784-3792. PMID 11724793
- ↑ a b C. P. Chang et al .: Positional importance of Pro53 adjacent to the Arg49-Gly50-Asp51 sequence of rhodostomin in binding to integrin alphaIIbbeta3. In: Biochem J 357, 2001, pp. 57-64. PMID 11415436 , PMC 1221928 (free full text)
- ↑ a b L. C. Knight and JE Romano: Functional expression of bitistatin, a disintegrin with potential use in molecular imaging of thromboembolic disease. In: Protein Expr Purif 39, 2005, pp. 307-319. PMID 15642483
- ↑ K. Stocker: Use of snake venom proteins in medicine. (PDF; 182 kB) In: Schweiz Med Wochenschr 129, 1999, pp. 205–216.
- ^ MA McLane et al: Disintegrins in health and disease. In: Front Biosci 13, 2008, pp. 6617-6637. PMID 18508683 (Review)
- ^ S. Swenson et al: Anti-angiogenesis and RGD-containing snake venom disintegrins. In: Curr Pharm Des 13, 2007, pp. 2860-2871. PMID 17979731 (Review)
- ↑ a b J. J. Calvette et al .: Identification of the disulfide bond pattern in albolabrin, an RGD-containing peptide from the venom of Trimeresurus albolabris: significance for the expression of platelet aggregation inhibitory activity. In: Biochemistry 30, 1991, pp. 5225-5229. PMID 2036389
- ↑ TF Huang et al.: Trigramin. A low molecular weight peptide inhibiting fibrinogen interaction with platelet receptors expressed on glycoprotein IIb-IIIa complex. In: J Biol Chem 262, 1987, pp. 16157-16163. PMID 3680247
- ↑ B. Rucinski et al .: Batroxostatin, an Arg-Gly-Asp-containing peptide from Bothrops atrox, is a potent inhibitor of platelet aggregation and cell interaction with fibronectin. In: Biochim Biophys Acta 1054, 1990, pp. 257-262. PMID 2207176
- ↑ J. Williams et al.: Elegantin and albolabrin purified peptides from viper venoms: homologies with the RGDS domain of fibrinogen and von Willebrand factor. In: Biochim Biophys Acta 1039, 1990, pp. 81-89. PMID 2191722
- ↑ A. Scaloni et al: Amino acid sequence and molecular modeling of glycoprotein IIb-IIIa and fibronectin receptor iso-antagonists from Trimeresurus elegans venom. In: Biochem J 319, 1996, pp. 775-782. PMID 8920980
- ↑ H. Minoux et al .: Structural analysis of the KGD sequence loop of barbourin, an alphaIIbbeta3-specific disintegrin. In; J Comput Aided Mol Des 14, 2000, pp. 317-327. PMID 10815769
- ↑ a b R. M. Scarborough et al.: Barbourin. A GPIIb-IIIa-specific integrin antagonist from the venom of Sistrurus m. barbouri. In: J Biol Chem 266, 1991, pp. 9359-9362. PMID 2033037
- ↑ JJ Calvetea et al .: The disulphide bond pattern of bitistatin, a disintegrin isolated from the venom of the viper Bitis arietans. In: FEBS Letters 416, 1997, pp. 197-202. PMID 9369214
- ↑ a b c C. Marcinkiewicz et al: Obtustatin: a potent selective inhibitor of alpha1beta1 integrin in vitro and angiogenesis in vivo. In: Cancer Res 63, 2003, pp. 2020-2023. PMID 12727812
- ↑ ZR Gan et al.: Echistatin. A potent platelet aggregation inhibitor from the venom of the viper, Echis carinatus. In: J Biol Chem 263, 1988, pp. 19827-19832. PMID 3198653
- ↑ J. Tian et al.: Inhibition of melanoma cell motility by the snake venom disintegrin eristostatin. In: Toxicon 49, 2007, pp. 899-908. PMID 17316731
- ↑ a b c L. C. Knight et al: Comparison of iodine-123-disintegrins for imaging thrombi and emboli in a canine model. In: J Nucl Med 37, 1996, pp. 476-482. PMID 8772651
- ↑ TF Huang et al: Halysin, an antiplatelet Arg-Gly-Asp-containing snake venom peptide, as fibrinogen receptor antagonist. In: Biochem Pharmacol 42, 1991, pp. 1209-1219. PMID 1888330
- ↑ T. Yasuda et al: Kistrin, a polypeptide platelet GPIIb / IIIa receptor antagonist, enhances and sustains coronary arterial thrombolysis with recombinant tissue-type plasminogen activator in a canine preparation. In: Circulation 83, 1991, pp. 1038-1047. PMID 1900221
- ↑ RS McDowell et al .: Mambin, a potent glycoprotein IIb-IIIa antagonist and platelet aggregation inhibitor structurally related to the short neurotoxins. In: Biochemistry 31, 1992, pp. 4766-4772. PMID 1591238
- ↑ TF Huang et al .: A potent antiplatelet peptide, triflavin, from Trimeresurus flavoviridis snake venom. In: Biochem J 277, 1991, pp. 351v357. PMID 1859363
literature
- RJ Gould et al: Disintegrins: a family of integrin inhibitory proteins from viper venoms. In: Proc Soc Exp Biol Med 195, 1990, pp. 168-171. PMID 2236100 (Review)
- JA Williams: Disintegrins: RGD-containing proteins which inhibit cell / matrix interactions (adhesion) and cell / cell interactions (aggregation) via the integrin receptors. In: Pathol Biol (Paris) 40, 1992, pp. 813-821. PMID 1484742 (Review)
- S. Niewiarowski et al: Disintegrins and other naturally occurring antagonists of platelet fibrinogen receptors. In: Semin Hematol 31, 1994, pp. 289-300. PMID 7831574 (Review)
- TF Huang: What have snakes taught us about integrins? In: Cell Mol Life Sci 54, 1998, pp. 527-540. PMID 9676572 (Review)
- RM Kini: Anticoagulant proteins from snake venoms: structure, function and mechanism. In: Biochem J 397, 2006, pp. 377-387. PMID 16831131 (review), PMC 1533313 (free full text)
- CH Yang: Inhibition of retinal pigment epithelial cell-induced tractional retinal detachment by disintegrins, a group of Arg-Gly-Asp-containing peptides from viper venom. In: Invest Ophthalmol Vis Sci 37, 1996, pp. 843-854. PMID 8603869
- MA McLane et al .: Disintegrins. In: Curr Drug Targets Cardiovasc Haematol Disord 4, 2004, pp. 327-355. PMID 1557895 (Review)
- X. Lu ua: Snake venom metalloproteinase containing a disintegrin-like domain, its structure-activity relationships at interacting with integrins. In: Curr Med Chem Cardiovasc Hematol Agents 3, 2005, pp. 249-260. PMID 15974889
- C. Barja-Fidalgo et al .: Disintegrins: integrin selective ligands which activate integrin-coupled signaling and modulate leukocyte functions. In: Braz J Med Biol Res 38, 2005, pp. 1513-1520. PMID 16172744 (Review)
- JA Williams: Disintegrins: RGD-containing proteins which inhibit cell / matrix interactions (adhesion) and cell / cell interactions (aggregation) via the integrin receptors. In: Pathol Biol (Paris) 40, 1992, pp. 813-821. PMID 1484742 (Review)
- K. Grimm: Induction of integrin-mediated synthesis and activation of matrix metalloproteinases by snake venom metalloproteinases in dermal fibroblasts. Dissertation, University of Cologne, 2003. urn : nbn: de: hbz: 38-13157
Web links
- T. Wolf: Snake venom against cancer. In: Die Welt from February 2, 2008
- T. Wolf: Snake venom against cancer, Alzheimer's and Parkinson's. In: Berliner Morgenpost from February 3, 2008