By: George Sitterley, BioFiles 2008, 3.8, 6.

BioFiles 2008, 3.8, 6.

Disintegrins are a family of cell surface receptors that mediate adhesion with other cells or with extracellular matrix proteins. Interaction with integrins regulates cell adhesion, cell spreading and migration, and change in cell shape. Some integrins have a restricted distribution while others can appear on many different cell types.1 Integrins are composed of a heterodimetric combination of α- and β-subunits. Their interaction with their ligands generally occurs via a common amino acid sequence, Arg-Gly-Asp (RGD), which represents the recognition site.

Disintegrins represent an interesting class of low molecular weight, RGD-containing, cysteine-rich peptides isolated from different snake venoms. They interact with β1- and β2-containing integrins, thus preventing their interaction with naturally occurring ligands. This group represents the most potent known inhibitors of some integrin functions.2,3

Disintegrins may serve as an important tool in basic research due to their various interesting activities. Distegrins bind specifically to the platelet glycoprotein receptor IIb/IIIa. Thus, they are competitive inhibitors of fibrinogen-dependent platelet aggregation induced by ADP, thrombin, epinephrine, and collagen.4,5,6 The quantity required for such inhibition is as low as nanomolar concentration in some models (e.g. kistrin, echistatin). By comparison, the concentration of disintegrins required to cause 50% inhibition of ADP-induced platelet aggregation in platelet-rich plasma was two to three times lower than the required concentration of the short RGDS peptide.6,7 The advantage of disintegrins as potent inhibitors of platelet aggregation in vivo is their short half-life and apparent non-toxicity.5,8 In addition to the activity mentioned, echistatin has been used as a potent inhibitor of bone resportion in cell culture at the nanomolar concentration.9 Other disintegrins inhibit murine melanoma cell metastasis and cell-matrix attachment and cell interaction with fibronectin.7,10,11

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  1. Hemler, M.E. inGuidebook to the Extracellular Matrix and Adhesion Proteins (1993), Kreis T. and Vale R. eds, Oxford University Press, Oxford, p. 143.
  2. Gould, R.J., et al., 1990) Proc. Soc. Exp. Biol. Med., 195: 168.
  3. Calvete, J.J., et al., (1992) FEBS, 309: 316.
  4. Dennis, M.S., et al., 0 989) Proc. Natl. Acad. Sci. USA, 87: 2471.
  5. Shebuski, R.J., et al., (1989) .1. Biol. Chem., 264: 21550.
  6. Musial, J., et al., (1990) Circulation, 82: 261.
  7. Rucinski, B., et al., (1990) Biochim. Biophys. Acta., 1054: 257.
  8. Cook, J.J., et al., (1989) Am. J. Physiol., 266: H1038.
  9. Sato, M., et al., (1990) J. Cell Biol., 111: 1713.
  10. Soszka, T., et al., (199 1) Exp. Cell Res., 196: 6.
  11. Knudsen, K.A., et al., (1988) Exp. Cell Res., 179: 42.

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