Abstract
Haemostasis is critical to normal health by preventing blood loss following injury and contributing to the maintenance of the vasculatory system, which supplies oxygen and nutrients to all parts of the body as well as performing other essential tasks. Thrombosis is the pathological variant leading to blockage of vessels, cutting off the blood supply to vital organs. Because of these important functions there is great interest in the development of new drugs that can prevent or cure thrombosis. Since platelet malfunction is a major contributor to thrombus formation and platelet inhibition reduces risk it is a prime target for new drug development. Many animals have developed naturally proteins or peptides that affect mammalian haemostasis. They use these mechanisms either to immobilise or kill prey in the case of snakes or to enhance blood feeding in the case of haematophagous insects or vampire bats. Often these proteins are effective in extremely small amounts. This book provides descriptions of a number of different classes of such proteins from snakes and insects and their target molecules on platelets, as a way of developing new approaches to anti-thrombotic drugs.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bell, W.R.J., 1997. Defibrinogenating enzymes. Drugs 54 (Suppl. 3), 18–30.
Brunner, H.R., Gavras, H., Turini, G.A., Waeber, B., Cappuis, P., McKinstry, D.N., 1978. Long-term treatment of hypertension in man by an orally active angiotensin-converting enzyme inhibitor. Clin. Sci. Mol. Med. Suppl. 4, 293 s–295 s.
Ferreira, S.H., Rocha e Silva, M., 1965. Potentiation of bradykinin and eledoisin by BPF (bradykinin potentiating factor) from Bothrops jararaca venom. Experientia 21, 347–349.
Fry, B.G., Vidal, N., Norman, J.A., Vonk, F.J., Scheib, H., Ramjan, S.F., Kuruppu, S., Fung, K., Hedges, S.B., Richardson, M.K., Hodgson, W.C., Ignjatovic, V., Summerhayes, R., Kochva, E., 2006. Early evolution of the venom system in lizards and snakes. Nature 439, 584–588.
Fry, B.G., Wroe, S., Teeuwisse, W., van Osch, M.J., Moreno, K., Ingle, J., McHenry, C., Ferrara, T., Clausen, P., Scheib, H., Winter, K.L., Greisman, L., Roelants, K., van der Weerd, L., Clemente, C.J., Giannakis, E., Hodgson, W.C., Luz, S., Martelli, P., Krishnasamy, K., Kochva, E., Kwok, H.F., Scanlon, D., Karas, J., Citron, D.M., Goldstein, E.J., McNaughtan, J.E., Norman, J.A., 2009. A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus (Megalania) priscus. Proc. Natl. Acad. Sci., U.S.A. 106, 8969–8974.
Hantgan, R.R., Stahle, M.C., 2009. Integrin priming dynamics: mechanisms of integrin antagonist-promoted αIIbβ3:PAC-1 molecular recognition. Biochemistry 48, 8355–8365.
Hartman, G.D., Egbertson, M.S., Halczenko, W., Laswell, W.L., Duggan, M.E., Smith, R.L., Naylor, A.M., Manno, P.D., Lynch, R.J., Zhang, G.X., Chang, C.T.C., Gould, R.J., 1992. Non-peptide fibrinogen receptor antagonists. 1. Discovery and design of exosite inhibitors. J. Med. Chem. 35, 4640–4642.
Kaplan, H.R., Cohen, D.M., Essenburg, A.D., Major, T.C., Mertz, T.E., Ryan, M.J., 1984. CI-906 and CI-907: new orally active nonsulfhydryl angiotensin-converting enzyme inhibitors. Fed. Proc. 43, 1326–1329.
Mousa, S.A., Kapil, R., Mu, D.X., 1999. Intravenous and oral antithrombotic efficacy of the novel platelet GPIIb/IIIa antagonist roxifiban (DMP754) and its free acid form, XV459. Arterioscler. Thromb. Vasc. Biol. 19, 2535–2541.
Ofosu, F.A., Fenton, J.W., II., Maraganore, J., Blajchman, M.A., Yang, X., Smith, L., Anvari, N., Buchanan, M.R., Hirsh, J., 1992. Inhibition of the amplification reactions of blood coagulation by site-specific inhibitors of alpha-thrombin. Biochem. J. 283, 893–897.
Römisch, J., Stöhr, H.A., Stauss, H., Koschinsky, R., Stüber, W., Pâques, E.P., 1994. Inhibition of in vitro clot growth by r-hirudin is more effective and longer sustained than by an analogous peptide. Thromb. Haemost. 71, 320–324.
Scarborough, R.M., Rose, J.W., Hsu, M.A., Phillips, D.R., Fried, V.A., Campbell, A.M., Nannizzi, L., Charo, I.F., 1991. Barbourin. A GPIIb-IIIa-specific integrin antagonist from the venom of Sistrurus m. barbouri. J. Biol. Chem. 266, 9359–9362.
Schoni, R., 2005. The use of snake venom-derived compounds for new functional diagnostic test kits in the field of haemostasis. Pathophysiol. Haemost. Thromb. 34, 234–240.
Sweet, C.S., Gross, D.M., Arbegast, P.T., Gaul, S.L., Britt, P.M., Ludden, C.T., Weitz, D., Stone, C.A., 1981. Antihypertensive activity of N-[(S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-Ala-L-Pro (MK-421), an orally active converting enzyme inhibitor. J. Pharmacol. Exp. Ther. 216, 558–566.
Tcheng, J.E., Harrington, R.A., Kottke-Marchant, K., Kleiman, N.S., Ellis, S.G., Kereiakes, D.J., Mick, M.J., Navetta, F.I., Smith, J.E., Worley, S.J., Miller, J.A., Joseph, D.M., Sigmon, K.N., Kitt, M.M., Dumee, C.P., Califf, R.M., Topol, E.J., 1995. Multicenter, randomized, double-blind, placebo-controlled trial of the platelet integrin glycoprotein IIb/IIIa blocker Integrelin in elective coronary intervention. IMPACT Investigators. Circulation 91, 2151–2157.
Tschudi, M., Lämmle, B., Alberio, L., 2009. Dosing lepirudin in patients with heparin-induced thrombocytopenia and normal or impaired renal function: a single-center experience with 68 patients. Blood 113, 2402–2409.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Clemetson, K.J., Kini, R.M. (2010). Introduction. In: Kini, R., Clemetson, K., Markland, F., McLane, M., Morita, T. (eds) Toxins and Hemostasis. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9295-3_1
Download citation
DOI: https://doi.org/10.1007/978-90-481-9295-3_1
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-9294-6
Online ISBN: 978-90-481-9295-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)