Toxins in thrombosis and haemostasis: Potential beyond imagination

Journal of Thrombosis and Haemostasis

Volumn 9, Issue 1 S, 2011, Pages 195-208

  Kini, R M ^a,b  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Apyrase; Collagen receptor; Disintegrins; Factor Xa inhibitor; Thrombin inhibitor

Indexed keywords

ALBOAGGREGIN B; ANCROD; ANTICOAGULANT PROTEIN; ANTITHROMBOCYTIC AGENT; ARGINYLGLYCYLASPARTIC ACID; BATROXOBIN; BITISCETIN; BOTHROALTERNIN; BOTHROJARACIN; BOTROCETIN; CONVULXIN; DISINTEGRIN; ECHISTATIN; EPTIFIBATIDE; FIBRINOGEN; HEMOSTATIC AGENT; LECTIN; MAMUSHIGIN; METALLOPROTEINASE; MUCETIN; PHOSPHOLIPASE A2; PROCOAGULANT; SCAFFOLD PROTEIN; SERINE PROTEINASE; SNAKE VENOM; TIROFIBAN; TOXIN; TRIGRAMIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; X BOX BINDING PROTEIN 1;

BINDING SITE; DRUG MECHANISM; HEMOSTASIS; HUMAN; ISCHEMIA; MEDICAL RESEARCH; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN TARGETING; RESTENOSIS; REVIEW; SALIVA; STRUCTURE ANALYSIS; THROMBOCYTE AGGREGATION; THROMBOSIS;

ANIMALS; ANTITHROMBINS; HEMOSTASIS; HUMANS; MODELS, MOLECULAR; SNAKE VENOMS; THROMBOSIS; TOXINS, BIOLOGICAL;

EID: 79960633933     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/j.1538-7836.2011.04279.x     Document Type: Review

References (120)

1. Andrews RK, Kamiguti AS, Berlanga O, Leduc M, Theakston RD, Watson SP. The use of snake venom toxins as tools to study platelet receptors for collagen and von Willebrand factor. Haemostasis 2001; 31: 155-72.
2. Perchuc AM, Wilmer M. Diagnostic use of snake venom components in the coagulation laboratory. In: Kini RM, Clemetson KJ, Markland FS, McLane MA, Morita T, eds. Toxins and Hemostasis: From Bench to Bedside. Dordrecht: Springer, 2010: 747-66.
3. Sweet CS, Gross DM, Arbegast PT, Gaul SL, Britt PM, Ludden CT, Weitz D, Stone CA. Antihypertensive activity of N-[(S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-Ala-LPro (MK-421), an orally active converting enzyme inhibitor. J Pharmacol Exp Ther 1981; 216: 558-66.
4. Tcheng JE, Harrington RA, Kottke-Marchant K, Kleiman NS, Ellis SG, Kereiakes DJ, Mick MJ, Navetta FI, Smith JE, Worley SJ, Miller JA, Joseph DM, Sigmon KN, Kitt MM, Dumee CP, Califf RM, Topol EJ. Multicenter, randomized, doubleblind, placebo-controlled trial of the platelet integrin glycoprotein IIb/IIIa blocker Integrelin in elective coronary intervention. IMPACT Investigators. Circulation 1995; 91: 2151-7.
5. Hartman GD, Egbertson MS, Halczenko W, Laswell WL, Duggan ME, Smith RL, Naylor AM, Manno PD, Lynch RJ, Zhang GX, Chang CTC, Gould RJ. Nonpeptide fibrinogen receptor antagonists. 1. Discovery and design of exosite inhibitors. J Med Chem 1992; 35: 4640-2.
6. Ofosu FA, Fenton JW II, Maraganore J, Blajchman MA, Yang X, Smith L, Anvari N, Buchanan MR, Hirsh J. Inhibition of the amplification reactions of blood coagulation by site-specific inhibitors of α-thrombin. Biochem J 1992; 283: 893-7.
7. Fox JW, Serrano SM. Insights into and speculations about snake venom metalloproteinase (SVMP) synthesis, folding and disulfide bond formation and their contribution to venom complexity. FEBS J 2008; 275: 3016-30.
8. Markland FS, Swenson S. Fibrolase and its evolution to clinical trials: a long and winding road. In: Kini RM, Clemetson KJ, Markland FS, McLane MA, Morita T, eds. Toxins and Hemostasis: From Bench to Bedside. Dordrecht: Springer, 2010: 409-27.
9. Yamada D, Sekiya F, Morita T. Prothrombin and factor X activator activities in the venoms of Viperidae snakes. Toxicon 1997; 35: 1581-9.
10. Takeda S, Igarashi T, Mori H, Araki S. Crystal structures of VAP1 reveal ADAMs' MDC domain architecture and its unique C-shaped scaffold. EMBO J 2006; 25: 2388-96.
11. Takeda S, Igarashi T, Mori H. Crystal structure of RVV-X: an example of evolutionary gain of specificity by ADAM proteinases. FEBS Lett 2007; 581: 5859-64.
12. Mizuno H, Fujimoto Z, Atoda H, Morita T. Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X. Proc Natl Acad Sci USA 2001; 98: 7230-4.
13. Kini RM. Serine proteases affecting blood coagulation and fibrinolysis from snake venoms. Pathophysiol Haemost Thromb 2005; 34: 200-4.
14. Mackessy SP. Thrombin-like enzymes in snake venoms. In: Kini RM, Clemetson KJ, Markland FS, McLane MA, Morita T, eds. Toxins and Hemostasis: From Bench to Bedside. Dordrecht: Springer, 2010: 519-57.
15. Stocker K, Barlow GH. The coagulant enzyme from Bothrops atrox venom (batroxobin). Meth Enzymol 1976; 45: 214-23.
16. Stocker K. Research, diagnostic and medicinal uses of snake venom enzymes. In: Bailey GS, ed. Enzymes from snake venom. Fort Collins, CO: Alaken Inc., 1998: 705-36.
17. Stocker K, Fischer H, Meier J, Brogli M, Svendsen L. Protein C activators in snake venoms. Behring Inst Mitt 1986; 79: 37-47.
18. Gempeler-Messina PM, Volz K, Buhler B, Muller C. Protein C activators from snake venoms and their diagnostic use. Haemostasis 2001; 31: 266-72.
19. Le Bonniec BF, Libraire J. Plasminogen activators from snake venoms. In: Kini RM, Clemetson KJ, Markland FS, McLane MA, Morita T, eds. Toxins and Hemostasis: From Bench to Bedside. Dordrecht: Springer, 2010: 371-92.
20. Santos BF, Serrano SM, Kuliopulos A, Niewiarowski S. Interaction of viper venom serine peptidases with thrombin receptors on human platelets. FEBS Lett 2000; 477: 199-202.
21. Kini RM. The intriguing world of prothrombin activators from snake venom. Toxicon 2005; 45: 1133-45.
22. Kwong S, Woods AE, Mirtschin PJ, Ge R, Kini RM. The recruitment of blood coagulation factor X into snake venom gland as a toxin: the role of promoter cis-elements in its expression. Thromb Haemost 2009; 102: 469-78.
23. 2 enzymes. Toxicon 2003; 42: 827-40.
24. 2. Eur J Biochem 1980; 112: 25-32.
25. 2 enzymes from snake venoms. Toxicon 2005; 45: 1147-61.
26. 2 by affinity binding studies and molecular bioinformatics. BMC Struct Biol 2007; 7: 82.
27. Gan ZR, Gould RJ, Jacobs JW, Friedman PA, Polokoff MA. Echistatin. A potent platelet aggregation inhibitor from the venom of the viper, Echis carinatus. J Biol Chem 1988; 263: 19827-32.
28. Huang TF, Holt JC, Kirby EP, Niewiarowski S. Trigramin: primary structure and its inhibition of von Willebrand factor binding to glycoprotein IIb/IIIa complex on human platelets. Biochemistry 1989; 28: 661-6.
29. Musial J, Niewiarowski S, Rucinski B, Stewart GJ, Cook JJ, Williams JA, Edmunds LH Jr. Inhibition of platelet adhesion to surfaces of extracorporeal circuits by disintegrins: RGD-containing peptides from viper venoms. Circulation 1990; 82: 261-73.
30. Proimos G. Platelet aggregation inhibition with glycoprotein IIb-IIIa inhibitors. J Thromb Thrombolysis 2001; 11: 99-110.
31. Clemetson KJ, Morita T, Kini RM. Registry of exogenous hemostatic factors of SSC of the ISTH. Scientific and standardization committee communications: classification and nomenclature of snake venom C-type lectins and related proteins. J Thromb Haemost 2009; 7: 360.
32. Morita T. C-type lectin-related proteins from snake venoms. Curr Drug Targets Cardiovasc Haematol Disord 2004; 4: 357-73.
33. Lu Q, Navdaev A, Clemetson JM, Clemetson KJ. Snake venom C-type lectins interacting with platelet receptors. Structure-function relationships and effects on haemostasis. Toxicon 2005; 45: 1089-98.
34. Ouyang C, Teng CM. Purification and properties of the anticoagulant principle of Agkistrodon acutus venom. Biochim Biophys Acta 1972; 278: 155-62.
35. Atoda H, Hyuga M, Morita T. The primary structure of coagulation factor IX/factor X-binding protein isolated from the venom of Trimeresurus flavoviridis. Homology with asialoglycoprotein receptors, proteoglycan core protein, tetranectin, and lymphocyte ε receptor for immunoglobulin E. J Biol Chem 1991; 266: 14903-11.
36. Zingali RB, Nogueira ACF. Bothrojaracin - a potent thrombin inhibitor. In: Kini RM, Clemetson KJ, Markland FS, McLane MA, Morita T, eds. Toxins and Hemostasis: From Bench to Bedside. Dordrecht: Springer, 2010: 179-99.
37. Ogilvie ML, Byl JW, Gartner TK. Platelet-aggregation is stimulated by lactose-inhibitable snake venom lectins. Thromb Haemost 1989; 62: 704-7.
38. Polgár J, Clemetson JM, Kehrel BE, Wiedemann M, Magnenat EM, Wells TN, Clemetson KJ. Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI collagen receptor. J Biol Chem 1997; 272: 13576-83.
39. Clemetson JM, Polgar J, Magnenat E, Wells TN, Clemetson KJ. The platelet collagen receptor glycoprotein VI is a member of the immunoglobulin superfamily closely related to FcαR and the natural killer receptors. J Biol Chem 1999; 274: 29019-24.
40. Murakami MT, Zela SP, Gava LM, Michelan-Duarte S, Cintra AC, Arni RK. Crystal structure of the platelet activator convulxin, a disulfide-linked α4β4 cyclic tetramer from the venom of Crotalus durissus terrificus. Biochem Biophys Res Commun 2003; 310: 478-82.
41. Horii K, Brooks MT, Herr AB. Convulxin forms a dimer in solution and can bind eight copies of glycoprotein VI: implications for platelet activation. Biochemistry 2009; 48: 2907-14.
42. 1 and GPIb in a phosphatidylinositol 3-kinase independent pathway. Biochem Biophys Res Commun 2001; 285: 689-95.
43. 1). Involvement of GPIa/IIa-associated src and protein tyrosine phosphorylation. J Biol Chem 2001; 276: 1643-52.
44. Navdaev A, Clemetson JM, Polgar J, Kehrel BE, Glauner M, Magnenat E, Wells TN, Clemetson KJ. Aggretin, a heterodimeric C-type lectin from Calloselasma rhodostoma (Malayan pit viper), stimulates platelets by binding to α2β1 integrin and glycoprotein Ib, activating Syk and phospholipase Cγ 2, but does not involve the glycoprotein VI/Fc receptor γ chain collagen receptor. J Biol Chem 2001; 276: 20882-9.
45. 1 integrin, glycoprotein VI, and the ligand-binding domain of glycoprotein Ibα. J Biol Chem 2001; 276: 25121-6.
46. Read MS, Shermer RW, Brinkhous KM. Venom coagglutinin: an activator of platelet aggregation dependent on von Willebrand factor. Proc Natl Acad Sci USA 1978; 75: 4514-8.
47. Brinkhous KM, Barnes DS, Potter JY, Read MS. von Willebrand syndrome induced by a Bothrops venom factor: bioassay for venom coagglutinin. Proc Natl Acad Sci USA 1981; 78: 3230-4.
48. Matsui T, Hamako J. Structure and function of snake venom toxins interacting with human von Willebrand factor. Toxicon 2005; 45: 1075-87.
49. Taniuchi Y, Kawasaki T, Fujimura Y, Suzuki M, Titani K, Sakai Y, Kaku S, Hisamichi N, Satoh N, Takenaka T, Handa M, Sawai Y. Flavocetin-A and -B, two high molecular mass glycoprotein Ib binding proteins with high affinity purified from Trimeresurus flavoviridis venom, inhibit platelet aggregation at high shear stress. Biochim Biophys Acta 1995; 1244: 331-8.
50. Wang R, Kini RM, Chung MC. Rhodocetin, a novel platelet aggregation inhibitor from the venom of Calloselasma rhodostoma (Malayan pit viper): synergistic and noncovalent interaction between its subunits. Biochemistry 1999; 38: 7584-93.
51. 2-I domain. J Mol Biol 2004; 341: 519-27.
52. 2 subunit proximal to the collagen binding site. Biochem J 2003; 15: 77-85.
53. Horii K, Okuda D, Morita T, Mizuno H. Structural characterization of EMS16, an antagonist of collagen receptor (GPIa/IIa) from the venom of Echis multisquamatus. Biochemistry 2003; 42: 12497-502.
54. Dormann D, Clemetson JM, Navdaev A, Kehrel BE, Clemetson KJ. Alboaggregin A activates platelets by a mechanism involving glycoprotein VI as well as glycoprotein Ib. Blood 2001; 97: 929-36.
55. Du XY, Magnenat E, Wells TN, Clemetson KJ. Alboluxin, a snake C-type lectin from Trimeresurus albolabris venom is a potent platelet agonist acting via GPIb and GPVI. Thromb Haemost 2002; 87: 692-8.
56. 1. Thromb Haemost 2001; 86: 1277-83.
57. Kini RM. Platelet aggregation and exogenous factors from animal sources. Curr Drug Targets Cardiovasc Haematol Disord 2004; 4: 301-25.
58. Kini RM. Molecular moulds with multiple missions: functional sites in three-finger toxins. Clin Exp Pharmacol Physiol 2002; 29: 815-22.
59. Kini RM, Doley R. Structure, function and evolution of three-finger toxins: mini proteins with multiple targets. Toxicon 2010; 56: 855-67.
60. McDowell RS, Dennis MS, Louie A, Shuster M, Mulkerrin MG, Lazarus RA. Mambin, a potent glycoprotein IIb-IIIa antagonist and platelet aggregation inhibitor structurally related to the short neurotoxins. Biochemistry 1992; 31: 4766-72.
61. Shiu JH, Chen CY, Chang LS, Chen YC, Chen YC, Lo YH, Liu YC, Chuang WJ. Solution structure of γ-bungarotoxin: the functional significance of amino acid residues flanking the RGD motif in integrin binding. Proteins 2004; 57: 839-49.
62. Kini RM, Haar NC, Evans HJ. Non-enzymatic inhibitors of coagulation and platelet aggregation from Naja nigricollis venom are cardiotoxins. Biochem Biophys Res Commun 1988; 150: 1012-6.
63. Banerjee Y, Mizuguchi J, Iwanaga S, Kini RM. Hemextin AB complex, a unique anticoagulant protein complex from Hemachatus haemachatus (African Ringhals cobra) venom that inhibits clot initiation and factor VIIa activity. J Biol Chem 2005; 280: 42601-11.
64. Ribeiro JM. Blood-feeding arthropods: live syringes or invertebrate pharmacologists? Infect Agents Dis 1995; 4: 143-52.
65. Francischetti IM, Sa-Nunes A, Mans BJ, Santos IM, Ribeiro JM. The role of saliva in tick feeding. Front Biosci 2009; 14: 2051-88.
66. Koh CY, Kini RM. Molecular diversity of anticoagulants from haematophagous animals. Thromb Haemost 2009; 102: 437-53.
67. Ledizet M, Harrison LM, Koskia RA, Cappello M. Discovery and pre-clinical development of antithrombotics from hematophagous invertebrates. Curr Med Chem Cardiovasc Hematol Agents 2005; 3: 1-10.
68. Warkentin TE, Greinacher A, Koster A. Bivalirudin. Thromb Haemost 2008; 99: 830-9.
69. Wong CK, White HD. Direct antithrombins: mechanisms, trials, and role in contemporary interventional medicine. Am J Cardiovasc Drugs 2007; 7: 249-57.
70. Mans BJ, Francischetti IMB. Sialomics perspectives on the evolution of blood-feeding behavior in arthropods: future therapeutics by natural design. In: Kini RM, Clemetson KJ, Markland FS, McLane MA, Morita T, eds. Toxins and Hemostasis: From Bench to Bedside. Dordrecht: Springer, 2010: 21-44.
71. Charlab R, Valenzuela JG, Rowton ED, Ribeiro JM. Toward an understanding of the biochemical and pharmacological complexity of the saliva of a hematophagous sand fly Lutzomyia longipalpis. Proc Natl Acad Sci USA 1999; 96: 15155-60.
72. Ribeiro JM, Francischetti IM. Role of arthropod saliva in blood feeding: sialome and post-sialome perspectives. Annu Rev Entomol 2003; 48: 73-88.
73. Valenzuela JG. Exploring tick saliva: from biochemistry to 'sialomes' and functional genomics. Parasitology 2004; 129 (Suppl.): S83-94.
74. Koh CY, Kazimirova M, Trimnell A, Takac P, Labuda M, Nuttall PA, Kini RM. Variegin, a novel fast and tight binding thrombin inhibitor from the tropical bont tick. J Biol Chem 2007; 282: 29101-13.
75. Koh CY, Kazimirova M, Nuttall PA, Kini RM. Noncompetitive inhibitor of thrombin. ChemBiochem 2009; 10: 2155-8.
76. Koh CY, Kini RM. Thrombin inhibitors from haematophagous animals. In: Kini RM, Clemetson KJ, Markland FS, McLane MA, Morita T, eds. Toxins and Hemostasis: From Bench to Bedside. Dordrecht: Springer, 2010: 239-54.
77. Waxman L, Smith DE, Arcuri KE, Vlasuk GP. Tick anticoagulant peptide (TAP) is a novel inhibitor of blood coagulation factor Xa. Science 1990; 248: 593-6.
78. Neeper MP, Waxman L, Smith DE, Schulman CA, Sardana M, Ellis RW, Schaffer LW, Siegl PK, Vlasuk GP. Characterization of recombinant tick anticoagulant peptide. A highly selective inhibitor of blood coagulation factor Xa. J Biol Chem 1990; 265: 17746-52.
79. Wei A, Alexander RS, Duke J, Ross H, Rosenfeld SA, Chang CH. Unexpected binding mode of tick anticoagulant peptide complexed to bovine factor Xa. J Mol Biol 1998; 283: 147-54.
80. Tuszynski GP, Gasic TB, Gasic GJ. Isolation and characterization of antistasin. An inhibitor of metastasis and coagulation. J Biol Chem 1987; 262: 9718-23.
81. Nutt E, Gasic T, Rodkey J, Gasic GJ, Jacobs JW, Friedman PA, Simpson E. The amino acid sequence of antistasin. A potent inhibitor of factor Xa reveals a repeated internal structure. J Biol Chem 1988; 263: 10162-7.
82. Dunwiddie C, Thornberry NA, Bull HG, Sardana M, Friedman PA, Jacobs JW, Simpson E. Antistasin, a leech-derived inhibitor of factor Xa. Kinetic analysis of enzyme inhibition and identification of the reactive site. J Biol Chem 1989; 264: 16694-9.
83. Crawley JT, Lane DA. The haemostatic role of tissue factor pathway inhibitor. Arterioscler Thromb Vasc Biol 2008; 28: 233-42.
84. Francischetti IM, Valenzuela JG, Andersen JF, Mather TN, Ribeiro JM. Ixolaris, a novel recombinant tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick, Ixodes scapularis: identification of factor X and factor Xa as scaffolds for the inhibition of factor VIIa/tissue factor complex. Blood 2002; 99: 3602-12.
85. Francischetti IM, Mather TN, Ribeiro JM. Penthalaris, a novel recombinant five-Kunitz tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick vector of Lyme disease, Ixodes scapularis. Thromb Haemost 2004; 91: 886-98.
86. Monteiro RQ, Rezaie AR, Bae JS, Calvo E, Andersen JF, Francischetti IM. Ixolaris binding to factor X reveals a precursor state of factor Xa heparin-binding exosite. Protein Sci 2008; 17: 146-53.
87. Mieszczanek J, Harrison LM, Vlasuk GP, Cappello M. Anticoagulant peptides from Ancylostoma caninum are immunologically distinct and localize to separate structures within the adult hookworm. Mol Biochem Parasitol 2004; 133: 319-23.
88. Mieszczanek J, Harrison LM, Cappello M. Ancylostoma ceylanicum anticoagulant peptide-1: role of the predicted reactive site amino acid in mediating inhibition of coagulation factors Xa and VIIa. Mol Biochem Parasitol 2004; 137: 151-9.
89. Murakami MT, Rios-Steiner J, Weaver SE, Tulinsky A, Geiger JH, Arni RK. Intermolecular interactions and characterization of the novel factor Xa exosite involved in macromolecular recognition and inhibition: crystal structure of human Gla-domainless factor Xa complexed with the anticoagulant protein NAPc2 from the hematophagous nematode Ancylostoma caninum. J Mol Biol 2007; 366: 602-10.
90. Giugliano RP, Wiviott SD, Stone PH, Simon DI, Schweiger MJ, Bouchard A, Leesar MA, Goulder MA, Deitcher SR, McCabe CH, Braunwald E, Monbouquette R, Nabors M, Wade W, Alshaher M, Van Hoose B, DeSpirito C, Vicari R, Howard M, Singh V, et al. Recombinant nematode anticoagulant protein c2 in patients with non-ST-segment elevation acute coronary syndrome: the ANTHEM-TIMI-32 trial. J Am Coll Cardiol 2007; 49: 2398-407.
91. Monteiro RQ, Andersen JF, Francischetti IMB. Hematophagy and inhibition of the extrinsic and intrinsic tenase complexes. In: Kini RM, Clemetson KJ, Markland FS, McLane MA, Morita T, eds. Toxins and Hemostasis: From Bench to Bedside. Dordrecht: Springer, 2010: 219-37.
92. Ribeiro JM, Schneider M, Guimaraes JA. Purification and characterization of prolixin S (nitrophorin 2), the salivary anticoagulant of the blood-sucking bug Rhodnius prolixus. Biochem J 1995; 308: 243-9.
93. Isawa H, Yuda M, Yoneda K, Chinzei Y. The insect salivary protein, prolixin-S, inhibits factor IXa generation and Xase complex formation in the blood coagulation pathway. J Biol Chem 2000; 275: 6636-41.
94. Andersen JF, Montfort WR. The crystal structure of nitrophorin 2. A trifunctional antihemostatic protein from the saliva of Rhodnius prolixus. J Biol Chem 2000; 275: 30496-503.
95. Francischetti IMB. Hematophagy and inhibition of platelet aggregation. In: Kini RM, Clemetson KJ, Markland FS, McLane MA, Morita T, eds. Toxins and Hemostasis: From Bench to Bedside. Dordrecht: Springer, 2010: 331-57.
96. Francischetti IM, Andersen JF, Ribeiro JM. Biochemical and functional characterization of recombinant Rhodnius prolixus platelet aggregation inhibitor 1 as a novel lipocalin with high affinity for adenosine diphosphate and other adenine nucleotides. Biochemistry 2002; 41: 3810-8.
97. Keller PM, Waxman L, Arnold BA, Schultz LD, Condra C, Connolly TM. Cloning of the cDNA and expression of moubatin, an inhibitor of platelet aggregation. J Biol Chem 1993; 268: 5450-6.
98. Mans BJ, Ribeiro JM. Function, mechanism and evolution of the moubatin-clade of soft tick lipocalins. Insect Biochem Mol Biol 2008; 38: 841-52.
99. Noeske-Jungblut C, Kratzschmar J, Haendler B, Alagon A, Possani L, Verhallen P, Donner P, Schleuning WD. An inhibitor of collagen-induced platelet aggregation from the saliva of Triatoma pallidipennis. J Biol Chem 1994; 269: 5050-3.
100. Morita A, Isawa H, Orito Y, Iwanaga S, Chinzei Y, Yuda M. Identification and characterization of a collagen-induced platelet aggregation inhibitor, triplatin, from salivary glands of the assassin bug, Triatoma infestans. FEBS J 2006; 273: 2955-62.
101. Cheng Y, Wu H, Li D. An inhibitor selective for collagen-stimulated platelet aggregation from the salivary glands of hard tick Haemaphysalis longicornis and its mechanism of action. Sci China C Life Sci 1999; 42: 457-64.
102. Connolly TM, Jacobs JW, Condra C. An inhibitor of collagen-stimulated platelet activation from the salivary glands of the Haementeria officinalis leech. I. Identification, isolation, and characterization. J Biol Chem 1992; 267: 6893-8.
103. van Zanten GH, Connolly TM, Schiphorst ME, de Graaf S, Slootweg PJ, Sixma JJ. Recombinant leech antiplatelet protein specifically blocks platelet deposition on collagen surfaces under flow conditions. Arterioscler Thromb Vasc Biol 1995; 15: 1424-31.
104. Cruz CP, Eidt J, Drouilhet J, Brown AT, Wang Y, Barnes CS, Moursi MM. Saratin, an inhibitor of von Willebrand factor-dependent platelet adhesion, decreases platelet aggregation and intimal hyperplasia in a rat carotid endarterectomy model. J Vasc Surg 2001; 34: 724-9.
105. Vilahur G, Duran X, Juan-Babot O, Casani L, Badimon L. Antithrombotic effects of saratin on human atherosclerotic plaques. Thromb Haemost 2004; 92: 191-200.
106. Harsfalvi J, Stassen JM, Hoylaerts MF, van Houtte E, Sawyer RT, Vermylen J, Deckmyn H. Calin from Hirudo medicinalis, an inhibitor of von Willebrand factor binding to collagen under static and flow conditions. Blood 1995; 85: 705-11.
107. 1, and von Willebrand factor. J Biol Chem 2007; 282: 26928-38.
108. Calvo E, Tokumasu F, Mizurini DM, McPhie P, Narum DL, Ribeiro JM, Monteiro RQ, Francischetti IM. Aegyptin displays high-affinity for the von Willebrand factor binding site (RGQOGVMGF) in collagen and inhibits carotid thrombus formation in vivo. FEBS J 2010; 277: 413-27.
109. Yoshida S, Sudo T, Niimi M, Tao L, Sun B, Kambayashi J, Watanabe H, Luo E, Matsuoka H. Inhibition of collagen-induced platelet aggregation by anopheline antiplatelet protein, a saliva protein from a malaria vector mosquito. Blood 2008; 111: 2007-14.
110. Wang X, Coons LB, Taylor DB, Stevens SE Jr, Gartner TK. Variabilin, a novel RGD-containing antagonist of glycoprotein IIb-IIIa and platelet aggregation inhibitor from the hard tick Dermacentor variabilis. J Biol Chem 1996; 271: 17785-90.
111. Karczewski J, Endris R, Connolly TM. Disagregin is a fibrinogen receptor antagonist lacking the Arg-Gly-Asp sequence from the tick, Ornithodoros moubata. J Biol Chem 1994; 269: 6702-8.
112. Mans BJ, Louw AI, Neitz AW. Savignygrin, a platelet aggregation inhibitor from the soft tick Ornithodoros savignyi, presents the RGD integrin recognition motif on the Kunitz-BPTI fold. J Biol Chem 2002; 277: 21371-8.
113. Francischetti IM, My Pham V, Mans BJ, Andersen JF, Mather TN, Lane RS, Ribeiro JM. The transcriptome of the salivary glands of the female western black-legged tick Ixodes pacificus (Acari: Ixodidae). Insect Biochem Mol Biol 2005; 35: 1142-61.
114. Calvo E, Pham VM, Marinotti O, Andersen JF, Ribeiro JM. The salivary gland transcriptome of the neotropical malaria vector Anopheles darlingi reveals accelerated evolution of genes relevant to hematophagy. BMC Genomics 2009; 10: 57.
115. Seymour JL, Henzel WJ, Nevins B, Stults JT, Lazarus RA. Decorsin. A potent glycoprotein IIb-IIIa antagonist and platelet aggregation inhibitor from the leech Macrobdella decora. J Biol Chem 1990; 265: 10143-7.
116. Krezel AM, Wagner G, Seymour-Ulmer J, Lazarus RA. Structure of the RGD protein decorsin: conserved motif and distinct function in leech proteins that affect blood clotting. Science 1994; 264: 1944-7.
117. Mazur P, Henzel WJ, Seymour JL, Lazarus RA. Ornatins: potent glycoprotein IIb-IIIa antagonists and platelet aggregation inhibitors from the leech Placobdella ornata. Eur J Biochem 1991; 202: 1073-82.
118. Karczewski J, Waxman L, Endris RG, Connolly TM. An inhibitor from the argasid tick Ornithodoros moubata of cell adhesion to collagen. Biochem Biophys Res Commun 1995; 208: 532-41.
119. Fry BG, Wüster W, Kini RM, Brusic V, Khan A, Venkataraman D, Rooney AP. Molecular evolution and phylogeny of elapid snake venom three-finger toxins. J Mol Evol 2003; 57: 110-29.
120. OmPraba G, Chapeaurouge A, Doley R, Devi KR, Padmanaban P, Venkatraman C, Velmurugan D, Lin Q, Kini RM. Identification of a novel family of snake venom proteins Veficolins from Cerberus rynchops using a venom gland transcriptomics and proteomics approach. J Proteome Res 2010; 9: 1882-93.