Toxins and Hemostasis

1. Antiplatelet proteins

   1. Front Matter

      Pages 267-267

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   2. The Discovery of Disintegrins

      • Tur-Fu Huang

      Pages 269-284

   3. Brief History and Molecular Determinants of Snake Venom Disintegrin Evolution

      • Juan J. Calvete

      Pages 285-300

   4. Anti-Angiogenesis and Disintegrins

      • Stephen Swenson, Radu Minea, Samuel Zidovetzki, Corey Helchowski, Fritz Costa, Francis S. Markland

      Pages 301-329

   5. Hematophagy and Inhibition of Platelet Aggregation

      • Ivo M.B. Francischetti

      Pages 331-357

   6. Snaclecs (Snake C-Type Lectins) that Inhibit Platelet Receptors

      • Kenneth J. Clemetson

      Pages 359-368

2. Antiplatelet proteins

   1. Front Matter

      Pages 369-369

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   2. Plasminogen Activators from Snake Venoms

      • Bernard F. Le Bonniec, Julie Libraire

      Pages 371-392

   3. Bat Plasminogen Activator: Desmoteplase – From Bat to Bench to Bedside of Stroke Victims

      • Wolfgang Söhngen, Karl-Uwe Petersen, Mariola Söhngen

      Pages 393-407

   4. Fibrolase and Its Evolution to Clinical Trials: A Long and Winding Road

      • Francis S. Markland, Stephen Swenson

      Pages 409-427

   5. Streptokinase

      • Paul E. Bock, Pablo Fuentes-Prior

      Pages 429-444

3. Procoagulant proteins

   1. Front Matter

      Pages 445-445

      PDF

   2. Activation of Factor X by Snake Venom Proteases

      • Jüri Siigur, Ene Siigur

      Pages 447-464

   3. Structural Aspects of the Factor X Activator RVV-X from Russell’s Viper Venom

      • Soichi Takeda

      Pages 465-484

   4. Snake Venom Prothrombin Activators – The History

      • Jan Rosing, Guido Tans

      Pages 485-499

   5. Origin and Evolution of Snake Venom Prothrombin Activators

      • Md. Abu Reza, R. Manjunatha Kini

      Pages 501-517

   6. Thrombin-Like Enzymes in Snake Venoms

      • Stephen P. Mackessy

      Pages 519-557

   7. Procoagulant Factors from Lonomia Caterpillars

      • Ana Marisa Chudzinski-Tavassi, Linda Christian Carrijo-Carvalho

      Pages 559-574

   8. Staphylocoagulase

      • Peter Panizzi, Heather K. Kroh, Pablo Fuentes-Prior, Paul E. Bock

      Pages 575-590

   9. Procoagulant Properties of Plant Latex Proteases

      • H.V. Shivaprasad, R. Rajesh, M. Yariswamy, B.S. Vishwanath

      Pages 591-603

Circulation of blood is vital for the survival of vertebrates, including man. Mainly, it plays an important role in carrying food nutrients and oxygen to every tissue and organ and in removing all waste products and carbon dioxide. Any imbalance in the hemostatic and cardiovascular systems can lead to death and severe debility. A number of animals have developed mechanisms to target these systems and exploit the vulnerability. In some species (for example, snakes), such mechanisms are used to immobilize and kill the victim/prey, whereas in others (for example, insects, such as leaches, mosquitoes and ticks), they are used to provide a continuous supply of blood. These mechanisms include, but are not limited to, procoagulant and anticoagulant actions that affect the coagulation cascade and platelet aggregation, as well as altering vasodilatory responses. In all these various animals, these mechanisms have evolved to perfection over millions of years to support their survival. In last 3-4 decades, due to the efforts of scientists from various backgrounds including biology, protein chemistry, molecular biology, pharmacology, hematology, and structural biology, significant progress in understanding the structure-function relationships, as well as the mechanism of action have been made in a number of exogenous factors that affect blood coagulation, platelet aggregation and vasodilation from various animals. These exogenous factors have contributed significantly to the development of research tools as well as providing new therapeutic agents. With the increase average age of the population coupled with changes in life style in recent years, there has been a significant increase in cardiovascular and hematological disorders. Thus scientists in both academic institutions as well as the pharmaceutical industry are developing better therapeutic agents to improve the quality of life. This impetus has lead to the search for novel agents from various sources that interfere withcardiovascular and hematalogical processes. Although at first glance exogenous factors appear to function as ‘villains’, several life-saving drugs have been developed based upon these factors. Such drugs or drug leads include those that inhibit the angiotensin converting enzymes (Captopril and Enalapril), that block platelet receptors (Eptifibatide and Tirofiban), or that digest thrombotic plugs (Alfimeprase and bat plasminogen activator) to name a few. Several new and exciting success stories are currently unfolding. In this book, recent studies on some of the exogenous factors that play crucial roles in cardiovascular and hematological disorders are reviewed in order to consolidate the efforts in this area of research and to recruit new, talented researchers. The 25-30 review chapters, each written by experts in their field, compiled herein are devoted to exogenous factors affecting platelet aggregation, anticoagulant and procoagulant proteins, fibrinolytic proteins and hypotensive agents (For details see, Contents of the Book). This book is intended to help to create elevated awareness and enthusiasm in the field of exogenous factors. I believe that this book will provide greater impetus to the search for novel proteins based on naturally occurring exogenous factors. This will be the first book dealing extensively with exogenous factors in the last 25 years. The book will provide a ready reference to the different approaches used to solve complex problems in protein chemistry and pharmacology of exogenous factors. The book will update our understanding of the structure-function relationships and mechanisms of action of exogenous factors and provide great insights into future directions for solving the remaining challenges.

• Anticoagulant proteins
• Blood coagulation inhibitors
• Hypertension
• Platelet aggregation
• Procoagulant proteins

• , Department of Biological Sciences, National University of Singapore, Singapore, Singapore

  R. Manjunatha Kini

• , Department of Haematology, University of Berne, Bern, Switzerland

  Kenneth J Clemetson

• , Biochemistry and Molecular Biology, University of Southern California, Los Angeles, USA

  Francis S. Markland

• , Medical Technology, University of Delaware, Newark, USA

  Mary Ann McLane

• , Biochemistry, Meiji Pharmaceutical University, Tokyo, Japan

  Takashi Morita

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