**2. Chemical composition and strategic importance of venoms**

Over 5000 years ago, the Mesopotamians used a cane with a serpent as an emblem of Nin‐ gizzida, the god of fertility, marriage and pests. In Christianity, the serpent has always been associated with evil because of the biblical allegory of Adam and Eve. There is also a biblical story in which Moses erected a post with a brazen serpent to release his people from the pla‐ gue of snakes. Throughout the development of Christianity, this symbol was transformed and the post became a tau.

But not always and not in all cultures, serpents were associated with evil. Many people be‐ lieved in the cure power of serpents, often associated with its venom. Indeed, the medicinal value of animal venoms has been known since Antiquity. The medicinal use of bee venom, apitoxin, is reported in ancient Egypt and in Europe and Asia history. Charlemagne and Ivan *the Terrible*, for example, would have used apitoxin to treat common diseases. The med‐ ical uses of scorpion and snake venoms are well documented in Chinese pharmacopoeia. In an Islamic traditional tale, Muhammed is sick and, in the face of no known cure, it allows the use of snake venom as a last resource.

To Greeks and Romans, the serpent was a symbol of cure because periodically abandons its old skin and seemingly reborn, in the same way that doctors remove the disease of the body and rejuvenate the men, and also because the serpent was a symbol of concentrated atten‐ tion, which was required to the curers. However, the association of serpents with cure may also be related to its venom, represented symbolically by herbs in the Greek-Roman mythol‐ ogy of Aesculapius, the god of medicine and cure. Called to assist Glaucus, who had been killed by lightning, Aesculapius saw a snake enter the room where he was, and killed it with his staff. Soon, a second serpent entered the room carrying herbs in its mouth, which depos‐ ited at the mouth of another dead serpent, making it back to life. Watching this scene, Aes‐ culapius decided to put the herbs into the Glaucus mouth, who also raised from dead. Since then, Aesculapius turned the serpent your pet guardianship. His staff with a coiled serpent became the symbol of modern medicine in a large number of countries and is present even in the banner of the World Health Organization (WHO).

However, despite the healing power of animal venoms be known for a long time, the sys‐ tematic investigation of venom components as natural sources for the generation of pharma‐ ceuticals was only performed over the past decades, after a peptide that potencialize bradykinin action was isolated from the venom of the Brazilian snake *Bothrops jararaca* [27]. This led to the development, in the 1950s, of the first commercial drug based on angiotensin I converting enzyme (ACE)-inhibitor (trade name captopril®), for the treatment of arterial hypertension and heart failure [28]. Prialt® (ziconotide) is another example of synthetic drug successfully isolated from an animal venom [11]. This is a synthetic non-opioid peptide, non-NSAID, non-local anesthetic calcium channel blocker, isolated from the secretions of the cone snail *Conus magus*. Prialt® is used for the alleviation of chronic intractable pain and is administered directly into the spinal cord, due to deep side effects or lack of efficacy when it is administered by the more common routes such as orally or intravenously.

of these new technologies, small peptides from animal venoms with unexplored biological activities started to be studied systematically, emerging, then, this new area of knowledge and scientific research called peptidomics. These molecules are potential candidates for new

An Integrated View of the Molecular Recognition and Toxinology - From Analytical Procedures to Biomedical

Over 5000 years ago, the Mesopotamians used a cane with a serpent as an emblem of Nin‐ gizzida, the god of fertility, marriage and pests. In Christianity, the serpent has always been associated with evil because of the biblical allegory of Adam and Eve. There is also a biblical story in which Moses erected a post with a brazen serpent to release his people from the pla‐ gue of snakes. Throughout the development of Christianity, this symbol was transformed

But not always and not in all cultures, serpents were associated with evil. Many people be‐ lieved in the cure power of serpents, often associated with its venom. Indeed, the medicinal value of animal venoms has been known since Antiquity. The medicinal use of bee venom, apitoxin, is reported in ancient Egypt and in Europe and Asia history. Charlemagne and Ivan *the Terrible*, for example, would have used apitoxin to treat common diseases. The med‐ ical uses of scorpion and snake venoms are well documented in Chinese pharmacopoeia. In an Islamic traditional tale, Muhammed is sick and, in the face of no known cure, it allows

To Greeks and Romans, the serpent was a symbol of cure because periodically abandons its old skin and seemingly reborn, in the same way that doctors remove the disease of the body and rejuvenate the men, and also because the serpent was a symbol of concentrated atten‐ tion, which was required to the curers. However, the association of serpents with cure may also be related to its venom, represented symbolically by herbs in the Greek-Roman mythol‐ ogy of Aesculapius, the god of medicine and cure. Called to assist Glaucus, who had been killed by lightning, Aesculapius saw a snake enter the room where he was, and killed it with his staff. Soon, a second serpent entered the room carrying herbs in its mouth, which depos‐ ited at the mouth of another dead serpent, making it back to life. Watching this scene, Aes‐ culapius decided to put the herbs into the Glaucus mouth, who also raised from dead. Since then, Aesculapius turned the serpent your pet guardianship. His staff with a coiled serpent became the symbol of modern medicine in a large number of countries and is present even

However, despite the healing power of animal venoms be known for a long time, the sys‐ tematic investigation of venom components as natural sources for the generation of pharma‐ ceuticals was only performed over the past decades, after a peptide that potencialize bradykinin action was isolated from the venom of the Brazilian snake *Bothrops jararaca* [27]. This led to the development, in the 1950s, of the first commercial drug based on angiotensin I converting enzyme (ACE)-inhibitor (trade name captopril®), for the treatment of arterial hypertension and heart failure [28]. Prialt® (ziconotide) is another example of synthetic drug

drugs or compounds with significant therapeutic actions.

and the post became a tau.

Applications

6

the use of snake venom as a last resource.

in the banner of the World Health Organization (WHO).

**2. Chemical composition and strategic importance of venoms**

The evolution of the venom secretion apparatus in animals is indeed an impressive biologi‐ cal achievement at the evolutionary point of view. Since venoms components result of bio‐ chemical and pharmacological refinement over a long period in evolutionary scale, they have been tuned for optimum activity by the natural evolution. Thus, nature has already prospected huge combinatorial libraries of potential therapeutic drugs. The biochemical evolution of proteins from salivary fluids or venom exocrine glands is remarkable, especial‐ ly when one considers the highly specialized functions of these proteins and its high specif‐ icity with respect to the target molecule.

Several classes of organic molecules have been described in venoms, such as alkaloids and acylpolyamines. However, the main constituents are indeed polypeptides. Venoms of cone snail and arthropods, such as spiders, scorpions and insects, to a lesser extent, seem to be mainly peptidic, while snakes produce protein rich venoms. Snake venoms contain a variety of proteases, which hydrolyze peptide bonds of proteins, nucleases, which hydrolyze phos‐ phodiester bonds of DNA, and neurotoxins, which disable signaling in the nervous system. The brown spider venom contains a variety of toxins, the most important of which is the tis‐ sue destruction agent sphingomyelinase D, present in the venom of all species of *Loxosceles* in different concentrations [29]. Only another spider genus (*Sicarius*) and several pathogenic bacteria are known to produce this enzyme.

Some venoms comprise several hundreds of components, which further expands its poten‐ tial as a source of new medicines. Many components of venoms affect the nervous system and modulate the generation and propagation of action potentials, acting on multiple molec‐ ular sites, which include central and peripheral neurons, axons, synapses and neuromuscu‐ lar junctions [30]. Many of these target receptors play important physiological roles or are associated with specific diseases. Therefore, the components of animal venoms are impor‐ tant biological tools for studying these receptors, and the discovery of molecules in venoms with selective activity for these receptors represents a very attractive approach to the search for new drugs. The venom components may therefore be probed for the development of new therapies for pain management [31], new anti-arrhythmic [32], anticonvulsant [33] or anxiolytic drugs [34], new antimicrobial agents [35-37] or pesticides [38, 39], etc. Even a sub‐ stance that causes priapism has been isolated from the venom of a Brazilian spider [40], be‐ coming a potential drug candidate to attend erectile dysfunction.

Another reason to study the composition of animal venoms is trying to seek more effective prophylaxis for envenomings. Doctors treat victims of venomous sting with serum, which is produced by injecting into an animal, such as sheep, horse, goat or rabbit, a small amount of specific venom. The animal's immune system responds to the target dose, producing anti‐ bodies to active molecules of the venom. These antibodies can then be isolated from the ani‐ mal's blood and used in envenoming treatment in other animals, including humans.

However, this treatment can be effectively used only a limited number of times for a partic‐ ular person, since that person will develop antibodies to neutralize the exogenous animal's antibodies used to produce the antiserum (antibodies antiantibodies). Even if that person does not suffer a severe allergic reaction to the antiserum, his own immune system can de‐ stroy the antiserum even before the antiserum destroys the venom toxins. Most people will never need an antiserum treatment throughout their lives. However, others, who work or live in risk areas habited by snakes or other venomous animals, such as agricultural areas for example, need that this treatment is available in public health network.

million different proteins, each one exerting a distinct role. Unlike the genome, which is relatively static, the proteome is constantly changing in response to tens of thousands of intra and extracellular environmental signals. The proteome varies with the nature of each tissue or organ, the cell development stage, the stress conditions to which the organism is subjected, the organism health state, the effects of drug treatment, etc. As such, the pro‐ teome is often defined as the proteins present in a sample (tissue, organism, cell culture,

Peptidomic Analysis of Animal Venoms http://dx.doi.org/10.5772/53773 9

The term proteomics consists of comprehensive and systematic study of all proteins present in a given cell state, which was made possible by the huge development of mass spectrome‐ try techniques over the past two decades. Proteomics and genomics run parallel and are in‐ terdependent. Genomics without proteomics is only an "alphabet soup", because it can only make inferences about their products (proteins). Moreover, proteomics requires genomics to identify the proteins expressed in a particular cell state. Briefly, genomics provides a static information of the various ways in which a cell may use its proteins, while proteomics gives a dynamic panorama of molecular diversity, showing not only which proteins are more or less expressed (or is not even expressed), but also how these proteins were modified and

Proteomic technologies can play an important role in new drugs discovery, new diagnos‐ tics and molecular medicine, because it is the connection between genes, proteins and dis‐ eases. For example, the discovery of defective proteins that cause specific diseases can help develop new drugs that either alter the shape of a defective protein or mimic its ac‐ tion. Most of the most popular drugs today either have proteinaceous nature or have a protein target. Through proteomics, one can create "custom" drugs, i.e., drugs specially designed for specific individuals. Such drugs are supposed to be more effective and cause fewer side effects. Another field to which proteomic studies can contribute is the biomark‐ ers discovery for specific diseases, whose overexpression (or depletion) would indicate, quite early, the disease development. For example, serum levels of prostate specific anti‐ gen (PSA) is commonly used in the diagnosis of prostate cancer in men, which makes PSA a biomarker for cancer. Unfortunately, however, the diagnosis based on a single pro‐ tein biomarker is not very reliable. Proteomics may help scientists to develop diagnostic tests that simultaneously analyze the expression of multiple proteins in order to improve

Over time, new study areas with the suffix "omics" have emerged, such as metabolomics, lipidomics, carbohydratomics, degradomics etc. The term venomics did not slow to appear, and today it is defined as the study of all components (protean or not protean) of a venom. The word peptidomics has also been proposed to set the study of the peptides (instead of proteins) of a cell type or a biological fluid, such as venom. According to Ivanov and Yatskin [42]: "structure and biologic function of the entire multitude of peptides circulating in living organisms, their organs, tissues, cells and fluids comprises the scope of peptidomics". For these authors, "these two multitudes of polypeptides (proteins and peptides) play a domi‐ nant role in the functioning of any cellular system, tissue or organ. They are intimately con‐

biological fluid, etc.) at a given point in time.

how these modifications affect its role in the cell theater.

the specificity and sensitivity of these tests.

Some treatments are done not with antiserum, but herbal. *Aristolochia rugosa* and *Aristolochia trilobata*, or angelic, are medicinal plants used in Western India and in Central and South America against snake and scorpion bites [41]. Aristolochic acid, produced by those plants, inhibits inflammation induced by immune complexes and non-immunological agents (carra‐ geenan or croton oil). It also inhibits the activity of phospholipases present in snake venoms (PLA2], forming a 1:1 complex with the enzyme. Phospholipases play an important role in the reactions cascade that lead to inflammatory response and pain. Therefore, its inhibition may reduce problems of scorpionism, snakebite and loxoscelism.
