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The Discovery of Disintegrins

  • Tur-Fu HuangEmail author
Chapter

Abstract

Disintegrins represent a class of low molecular weight, Arg-Gly-Asp(RGD)/Lys-Gly-Asp(KGD)-containing, cysteine-rich polypeptides derived from venoms of various viper snakes. They bind to various integrins (e.g. αIIbβ3, αvβ3, α5β1 and others) expressed on cell membrane surface, with various degrees of affinity and specificity. Disintegrins were originally discovered as antiplatelet agents by acting as platelet membrane αIIbβ3 antagonists. However, they also have been found to bind αvβ3, α5β1 or α4β1 expressed on endothelial cells, fibroblasts, phagocytes, and tumor cells, thus affecting cell-matrix and cell-cell interaction. The homologous molecular structure among disintegrin, snake venom metalloproteinase (SVMP), and ADAM (a disintegrin and metalloproteinase) reveals their evolutionary relationship. Based on the structure-activity relationship of these molecules and integrins, the potential applications of these disintegrins and their derivatives are briefly discussed in field of arterial thrombosis, cell adhesion, cell migration, angiogenesis, inflammation, and tumor metastasis.

Keywords

Platelet Aggregation Snake Venom Inhibit Platelet Aggregation Platelet Membrane Glycoprotein Experimental Metastasis Model 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

I would like to thank my Ph.D. thesis advisor, Dr. C. Ouyang, who encouraged me to stick on the topic entitled “Platelet inhibitory components in Trimeresurus gramineus venom” from which the first disintegrin Trigramin was discovered. Next, I also thank my partners Drs. S. Niewiarowski and Dr. J.C. Holt, Thrombosis Research Center, Temple University School of Medicine, who helped me to elucidate the primary sequence of the first naturally-occurring RGD-containing disintegrin, its primary target of platelet αIIbβ3,and its in vivo antithrombotic activity. Thanks to my graduate students and assistants for the devoted pursuit of the mysterious biology of snake venom. Finally, I appreciate the long-term financial support from National Science Council of Taiwan.

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© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Institute of Pharmacology, College of Medicine, National Taiwan UniversityTaipeiTaiwan

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