Preface

Molecular Toxinology has been consolidated as a scientific field focused on the intertwined description of ecological, biochemical, clinical, pharmacological and structural aspects of an‐ imal toxins. In an inquiring biological world, where the practical scientific responses are giv‐ en ultimately to improve the human health, animal toxins have arisen as an invaluable source for the discovery of therapeutic peptides and proteins. Both basic and applied re‐ search in academy and pharmaceutical industries are granted and benefited from million of years of natural history by which families of toxins in animal venoms have evolved and were improved in terms of selectivity and target specificity. Another advantage is that na‐ ture has selected several toxin structures and scaffolds to act effectively as poison but indeed have similar counterparts in the human body. No matter if organic or polypeptide, animal toxins rely on specific chemical interactions with their partner molecule to exert their biolog‐ ical actions.

Obviously, better the comprehension of how molecules interact and discriminate (recognize) their target, better the benefits we can achieve for rational exploration of the bioactive pepti‐ des and polypeptides as therapeutics. In this respect, a deep investigation of the molecular mechanism of interaction and recognition by which a given polypeptide acts as ligand or target molecule offers a window of opportunities for the pharmaceutical industry and clini‐ cal medicine.

This book is dedicated to present to the reader selected elegant examples of two intercon‐ nected themes - molecular recognition and toxinology–concerning to the integration be‐ tween analytical procedures and biomedical applications. With this aim, the book is divided in three sections, where the first combines chapters on molecular toxinology, the second deals on molecular cloning and genetics, and the third brings into focus basic and applied works on molecular recognition.

Thus, by means of proteomic and pharmacological concepts, Cunha's group (Chapter 1) and Fernandes-Pedrosa (Chapter 2) describe several examples of venom toxins from the main poisonous animal groups and illustrate the potential application of isolated venom compo‐ nents to modulate physiological and pathological processes, particularly, in mammals. In Chapter 3, Mortari and Siqueira Cunha present a comprehensive review concerning to the arthropod neurotoxic polypeptides useful for target-driven drug discovery, and in Chapter 4 Giuliatti shows in detail how to apply distinct computational methods to elaborate threedimensional protein models and search for binders and ligands. Lameu and collaborators, in Chapter 5, review the multiple biological roles of venom bradikinin potetiating peptides–a component of kallikrein-kinin system–and the importance of these molecules in programs of drug development for the treatment of cardiovascular diseases. In Chapter 6, Yanomine and co-workers discuss about serine proteases from snake venom, taking into account the clon‐ ing, expression and use of this class of thrombin-like enzymes in controlling coagulopathies. In Chapter 7, Chudzinski-Tavassi's group paradigmatically covers robust analytical proce‐ dures to understand the Lonomia obliqua (caterpillar) envenomation, compositional deter‐ mination of bristle secretion, and biomedical application of its components on blood coagulation system. In a moment that several species of hymenoptera have their genome sequenced and annotated, Torres and co-authors bring to view, in Chapter 8, the current status and recent progress on the venom from ants, dedicating particular attention to the giant ant Dinoponera quadriceps. Connecting the molecular mechanism by which toxins in‐ duce tissue damage, Bruzan and collaborators (Chapter 9) elegantly discuss the role of miR‐ NA in the mechanism of intoxication caused by microcystin - a hepatotoxin produced by cyanobacteria.

ating recognition of molecules involves the application of potentiometry, as discussed by Radecki and Radecka, in Chapter 20. Closing the section three, Akitsu and Kominato bring into view the backgrounds of conformational changes occurring in consequence of molecu‐ lar recognition based on Schiff-base interaction. This principle can be applicable for spectro‐

I hope the readers will enjoy the selected and interconnected themes compiled here and that the chapters in this book will serve as useful reference for productive research and techno‐

I am very thankful to all authors for their contribution and sharing their knowledge, what surely is the result from constant and dedicated works. I manifest my gratitude to InTech

Universidade Federal do Ceara, Instituto de Ciencias do Mar - Labomar,

**Dr. Gandhi Radis-Baptista**

Brazil

Preface XI

scopic analysis and docking studies of metal-Schiff base complexes in proteins.

editorial office for making possible the concretization of this book project.

logical application.

Section two is opened with a work written by Perez de la Lastra et al. (Chapter 10) devoted to the identification of key components from vulture immune system involved in the neu‐ tralization of noxious microorganisms taking during carcass feeding. Related to host mecha‐ nisms of detoxification and control of disease-causing plague's vector, the article authored by Shahein et al. (Chapter 11) introduces the genetic, structural and functional characteris‐ tics of GST from ticks and its amenability to serve as an antigen for parasite killing using anti-tick vaccines. In connection, Castillo & Porta (Chapter 12) focus on presenting concepts and practice of preparing structurally modified recombinant allergens for diagnosis and al‐ lergen-specific immunotherapy to treat allergy syndrome. In biotechnology, different bio‐ logical platforms are used for genome modification and developed for recombinant protein expression. The review article (Chapter 13) by Murakami brings into focus the recent advan‐ ces in genetic transformation of macroalgae–a photosynthetic biological system of high eco‐ nomic, industrial and medical importance. Closing the section two, Noriyuki and collaborators report, in Chapter 14, the genetic diversity and population balance of Hotoke loach in rivers from rural area of Japan, bringing to discussion an actual ecological case that can be applicable as model for the evaluation of population status and genetic background of other endangered species of animals.

Section three starts (Chapter 15) with the examination of the mechanistic and structural characteristics of molecular recognition between HIV-1 integrase and its inhibitor raltegra‐ vir, by Tchertanov and Arora. This survey sets the basis for target-based drug discovery and clinical application of highly specific allosteric inhibitor in HIV therapy. In Chapter 16, Fier‐ ro and collaborators present theoretical and original data from protein crystal structure and computational molecular modelling to evaluate ligand-binding sites of monoamine oxidases and experimentally test several selective inhibitors. Hibino and co-authors (Chapter 17) treat sharply on a powerful and sophisticated technology to investigate and quantify the ligand association/dissociation with their respective receptors based on single-molecule imaging (SMI). The authors offer some examples of the actual use of SMI in Life Sciences and its ap‐ plicability in the field of Toxinology. The molecular interaction and recognition between sac‐ charides and polypeptides play a crucial role in biological process and signaling. In Chapter 18, Miura and collaborators exemplify several aspects of sugar-protein discrimination and interaction, discussing the fabrication of glycopolymeric biomaterials for analytical and nanotechnological purposes. In Chapter 19, Khalafi and Rafiee present fundaments of how spectral changes of cyclodextrin are observed and illustrate practical uses of this system in molecular recognition of distinct compounds, including toxins. Another technique of evalu‐ ating recognition of molecules involves the application of potentiometry, as discussed by Radecki and Radecka, in Chapter 20. Closing the section three, Akitsu and Kominato bring into view the backgrounds of conformational changes occurring in consequence of molecu‐ lar recognition based on Schiff-base interaction. This principle can be applicable for spectro‐ scopic analysis and docking studies of metal-Schiff base complexes in proteins.

co-workers discuss about serine proteases from snake venom, taking into account the clon‐ ing, expression and use of this class of thrombin-like enzymes in controlling coagulopathies. In Chapter 7, Chudzinski-Tavassi's group paradigmatically covers robust analytical proce‐ dures to understand the Lonomia obliqua (caterpillar) envenomation, compositional deter‐ mination of bristle secretion, and biomedical application of its components on blood coagulation system. In a moment that several species of hymenoptera have their genome sequenced and annotated, Torres and co-authors bring to view, in Chapter 8, the current status and recent progress on the venom from ants, dedicating particular attention to the giant ant Dinoponera quadriceps. Connecting the molecular mechanism by which toxins in‐ duce tissue damage, Bruzan and collaborators (Chapter 9) elegantly discuss the role of miR‐ NA in the mechanism of intoxication caused by microcystin - a hepatotoxin produced by

Section two is opened with a work written by Perez de la Lastra et al. (Chapter 10) devoted to the identification of key components from vulture immune system involved in the neu‐ tralization of noxious microorganisms taking during carcass feeding. Related to host mecha‐ nisms of detoxification and control of disease-causing plague's vector, the article authored by Shahein et al. (Chapter 11) introduces the genetic, structural and functional characteris‐ tics of GST from ticks and its amenability to serve as an antigen for parasite killing using anti-tick vaccines. In connection, Castillo & Porta (Chapter 12) focus on presenting concepts and practice of preparing structurally modified recombinant allergens for diagnosis and al‐ lergen-specific immunotherapy to treat allergy syndrome. In biotechnology, different bio‐ logical platforms are used for genome modification and developed for recombinant protein expression. The review article (Chapter 13) by Murakami brings into focus the recent advan‐ ces in genetic transformation of macroalgae–a photosynthetic biological system of high eco‐ nomic, industrial and medical importance. Closing the section two, Noriyuki and collaborators report, in Chapter 14, the genetic diversity and population balance of Hotoke loach in rivers from rural area of Japan, bringing to discussion an actual ecological case that can be applicable as model for the evaluation of population status and genetic background

Section three starts (Chapter 15) with the examination of the mechanistic and structural characteristics of molecular recognition between HIV-1 integrase and its inhibitor raltegra‐ vir, by Tchertanov and Arora. This survey sets the basis for target-based drug discovery and clinical application of highly specific allosteric inhibitor in HIV therapy. In Chapter 16, Fier‐ ro and collaborators present theoretical and original data from protein crystal structure and computational molecular modelling to evaluate ligand-binding sites of monoamine oxidases and experimentally test several selective inhibitors. Hibino and co-authors (Chapter 17) treat sharply on a powerful and sophisticated technology to investigate and quantify the ligand association/dissociation with their respective receptors based on single-molecule imaging (SMI). The authors offer some examples of the actual use of SMI in Life Sciences and its ap‐ plicability in the field of Toxinology. The molecular interaction and recognition between sac‐ charides and polypeptides play a crucial role in biological process and signaling. In Chapter 18, Miura and collaborators exemplify several aspects of sugar-protein discrimination and interaction, discussing the fabrication of glycopolymeric biomaterials for analytical and nanotechnological purposes. In Chapter 19, Khalafi and Rafiee present fundaments of how spectral changes of cyclodextrin are observed and illustrate practical uses of this system in molecular recognition of distinct compounds, including toxins. Another technique of evalu‐

cyanobacteria.

X Preface

of other endangered species of animals.

I hope the readers will enjoy the selected and interconnected themes compiled here and that the chapters in this book will serve as useful reference for productive research and techno‐ logical application.

I am very thankful to all authors for their contribution and sharing their knowledge, what surely is the result from constant and dedicated works. I manifest my gratitude to InTech editorial office for making possible the concretization of this book project.

> **Dr. Gandhi Radis-Baptista** Universidade Federal do Ceara, Instituto de Ciencias do Mar - Labomar, Brazil

**Section 1**

**Molecular Toxinology**

**Molecular Toxinology**

**Chapter 1**

**Peptidomic Analysis of Animal Venoms**

The last two decades have witnessed a growing interest in the discovery of new chemical and pharmacological substances of animal origin. Pharmacological tests of toxins obtained from animal venoms revealed its effects on central nervous system, mainly acting on ion channels in heart, intestine, in vascular permeability, etc. Potential applications of these sub‐ stances have been proposed ranging from human disease treatment to plague control of ag‐ ricultural interest. In this scenario, the peptidomic analysis has played an increasingly

Venomous organisms are widespread throughout the animal kingdom, comprising more than 100,000 species distributed in all major phyla. Virtually all ecosystems on Earth have venomous or poisonous organisms. Venoms represent an adaptive trait, and an example of convergent evolution. They are truly mortal cocktails, comprising unique mixtures of pepti‐ des and proteins naturally tailored by natural selection to operate in defense or attack sys‐ tems, for the prey or the victim. Venoms represent an enormous reservoir of bioactive compounds able to cure diseases that do not respond to conventional therapies. Darwinian evolution of animal venoms has accumulated in nature a wide variety of biological fluids which resulted in a true combinatorial libraries of hundreds of thousands of molecules po‐

Venom is a general term which refers to a variety of toxins used by certain animals that inoculate its victims through a bite, a sting or other sharp body feature. Venoms of verte‐ brates and invertebrates contain a molecular diversity of proteins and peptides, and other classes of substances, which together form an arsenal of highly effective agents, paralyz‐ ing and lethal, mainly used for predation and defense. We must distinguish venom from poison, which is ingested or inhaled by the victim, being absorbed by its digestive system or respiratory system. Animal venoms, in contrast, are administered directly into the lym‐

> © 2013 Cunha; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

© 2013 Cunha; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

distribution, and reproduction in any medium, provided the original work is properly cited.

Additional information is available at the end of the chapter

tentially active and pharmacologically useful.

Ricardo Bastos Cunha

http://dx.doi.org/10.5772/53773

**1. Introduction**

important role.
