**7. Biotechnological and pharmacological applications of ant, centipede and caterpillar venom toxins**

Ant, centipede and caterpillar venoms have not been studied so extensively as the venoms of snakes, scorpions and spiders. Ant venoms are rich in the phospholipase A2 and B, hya‐ luronidase, and acid and alkaline phosphatase as well as in histamine itself [227]. Centipede venoms have been poorly characterized in the literature. Studies have reported in centipede venoms the presence of esterases, proteinases, alkaline and acid phosphatases, cardiotoxins, histamine, and neurotransmitter releasing compounds in *Scolopendra* genus venoms [228]. Among the most studied caterpillar venoms are *Lonomia obliqua* and *Lonomia achelous* ven‐ oms, which cause similar clinical effects [229]. Based on cDNA libraries, was possible to identify several proteins from *L. obliqua,* such as cysteine proteases, group III phospholipase A2, C-type lectins, lipocalins, in addition to protease inhibitors including serpins, Kazal-type inhibitors, cystatins and trypsin inhibitor-like molecules [230].

### **7.1. Toxins acting on cardiovascular system**

A study showed that the *Lonomia obliqua* caterpillar bristles extract (LOCBE) directly releas‐ es kinin from low-molecular weight kininogen, being suggested that kallikrein-kinin system plays a role in the edematogenic and hypotensive effects during *L. obliqua* envenomation [231].

#### **7.2. Toxins acting on hemostasis**

phosphatidylinositol-(3,4)-bisphosphate was more effective in the blocking of tumor cell growth [218]. New peptides have been isolated from bee venom and tested in tumor cells, exhibiting promising activities in the treatment of cancer. Lasioglossins isolated from the venom of the bee *Lasioglossum laticeps* exhibited potency to kill various cancer cells *in vitro* [219]. Briefly the bee venom acts inhibiting cell proliferation and promoting cell death by different means: increasing Ca2+ influx; inducing cytochrome C release; binding calmodulin; decreasing or increasing the expression of proteins that control cell cycle or activating PLA2, causing damage to cell membranes interfering in the apoptotic pathway [220]. Among po‐ tential anticancer compounds, one of the most studied is mastoparan, peptide isolated from wasp venom that has been reported to induce a potent facilitation of the mitochondrial per‐ meability transition. It should be noted that this recognized action of mastoparan is marked at concentrations <1 μM [221]. Two novel mastoparan peptides, Polybia-MP-II e Polybia-MP-III isolated from venom of the social wasp *Polybia paulista*, exhibited hemolytic activity on erythrocytes [222]. Polybia-MPI, also was purified from the venom of the social wasp *P. paulista*, synthesized and studied its antitumor efficacy and cell selectivity. Results revealed that polybia-MPI exerts cytotoxic and antiproliferative efficacy by pore formation and have

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

Bee venom inhibits insulitis and development of diabetes in non-obese diabetic (NOD) mice. The cumulative incidence of diabetes at 25 weeks of age in control was 58% and NOD mice bee venom treated was 21% [224]. Mastoparan, component of wasp venom, is known to af‐ fect phosphoinositide breakdown, calcium influx, exocytosis of hormones and neurotrans‐ mitters and stimulate the GTPase activity of guanine nucleotide-binding regulatory proteins [225]. Thus, it is reported in the literature that mastoparan stimulates insulin secretion in hu‐ man, as well as in rodent. Furthermore, glucose and alpha-ketoisocaproate (alfa-KIC) in‐

**7. Biotechnological and pharmacological applications of ant, centipede**

Ant, centipede and caterpillar venoms have not been studied so extensively as the venoms of snakes, scorpions and spiders. Ant venoms are rich in the phospholipase A2 and B, hya‐ luronidase, and acid and alkaline phosphatase as well as in histamine itself [227]. Centipede venoms have been poorly characterized in the literature. Studies have reported in centipede venoms the presence of esterases, proteinases, alkaline and acid phosphatases, cardiotoxins, histamine, and neurotransmitter releasing compounds in *Scolopendra* genus venoms [228]. Among the most studied caterpillar venoms are *Lonomia obliqua* and *Lonomia achelous* ven‐ oms, which cause similar clinical effects [229]. Based on cDNA libraries, was possible to identify several proteins from *L. obliqua,* such as cysteine proteases, group III phospholipase A2, C-type lectins, lipocalins, in addition to protease inhibitors including serpins, Kazal-type

relatively lower cytotoxicity to normal cells [223].

crease the mastoparan-stimulated insulin secretion [226].

inhibitors, cystatins and trypsin inhibitor-like molecules [230].

**6.7. Toxins with insulin releasing activity**

Applications

40

**and caterpillar venom toxins**

There are numerous studies in literature reporting the effects on the hemostatic system of toxins from caterpillars. The effect of a crude extract of spicules from *Lonomia obliqua* cater‐ pillar on hemostasis was found to activate both prothrombin and factor X [232]. Lopap is a prothrombin activator isolated from the bristles of *L. obliqua* caterpillar. Lopap demonstrated ability to induce activation, expression of adhesion molecules and to exert an anti-apoptotic effect on human umbilical vein endothelial cells [233]. Lonofibrase, an α-fibrinogenase from *L. obliqua* was isolated from venomous secretion [234]. Losac, a protein with procoagulant activity, which acts as a growth stimulator and an inhibitor of cellular death for endothelial cells, was purified of the bristle extract of *L. obliqua*. Losac may have biotechnological appli‐ cations, including the reduction of cell death and consequently increased productivity of an‐ imal cell cultures [235]. Lonomin V, serine protease isolated from *Lonomia achelous* caterpillar, inhibited platelet aggregation, probably caused by the degradation of collagen. It is emphasized that Lonomin V shows to be a potentially useful tool for investigating cellmatrix and cell-cell interactions and for the development of antithrombotic agents in terms of their anti-adhesive activities [236]. The venom from the tropical ant, *Pseudomyrmex triplar‐ inus*, inhibited arachidonic acid and induced platelet aggregation, suggesting that venom prevented the action of prostaglandins. The venom was fractionated and factor F (adeno‐ sine) with antiplatelet activity were detected [237].

### **7.3. Toxins with antibiotic activity**

Venom alkaloids from *Solenopsis invicta,* fire ant, inhibit the growth of Gram-positive and Gram-negative bacteria and presumably act as a brood antibiotic. Peptides named poneri‐ cins were identified from the venom of ant *Pachycondyla goeldii*. Fifteen peptides were classi‐ fied into three different families according to their primary structure similarities: ponericins G, W, and L. Ponericin G1, G3, G4 and G6 demonstrated antimicrobial activity. Ponericins G share about 60% sequence similarity with cecropins and these have a broad spectrum of ac‐ tivity against bacteria. Peptides family W shares about 70% sequence similarity with Gae‐ gurin 5 (*Rana rugosa*) and melittin (discussed in previous topics). Gaegurin 5 exhibits a broad spectrum of antimicrobial action against bacteria, fungi, and protozoa and has very little hemolytic action. The ponericin L2 from the third family has only an antibacterial ac‐ tion, and shares important sequence similarities with dermaseptin 5, which has strong anti‐ microbial action against bacteria, yeast, fungi, and protozoa [238]. A cytotoxic peptide from the venom of the ant *Myrmecia pilosula*, Pilosulin 1, was identified as a potential novel anti‐ microbial peptide sequence. It outlined a potent and broad spectrum antimicrobial activity including standard and multi-drug resistant gram-positive and gram-negative bacteria and

*Candida albicans* [239]. Two antimicrobial peptides from centipede venoms, scolopin 1 and 2 were identified from venoms of *Scolopendra subspinipes mutilan* [240].

NP Anti-hypertensive agent [4]

NP Anti-hypertensive agent [23]

BPP Anti-hypertensive agent [17]

DNP Anti-hypertensive agent: natriuretic peptide [19]

[27]

43

http://dx.doi.org/10.5772/52380

[27]

[25]

[26]

[29]

[147]

[167]

[11]

[11]

[185]

C10S2C2 Anti-hypertensive drug: L-type Ca2+channels

Ca2+channels blocker

Ca2+channels blocker

Ca2+channels blocker

Ca2+channels blocker

GsMtx-4 Blocks cardiac stretch-activated ion channels

exciting substance

exciting substance

arrhythmic agent

Cinobufagin NaK+ATPase inhibitor [165]

NP Anti-hypertensive agent [22]

NP Anti-hypertensive agent [21]

BPP Anti-hypertensive agent [98]

and suppresses atrial fibrillation in rabbits

Hypotensive agent [168]

*Bungarus flaviceps* NP Anti-hypertensive agent [24]

Toxins from Venomous Animals: Gene Cloning, Protein Expression and Biotechnological Applications

blocker

S4C8 Anti-hypertensive agent: L-type

Calciseptine Anti-hypertensive agent: L-type

FS2 toxins Anti-hypertensive agent: L-type

*Micrurus corallinus* NP Anti-hypertensive agent [20]

Stejnihagin Anti-hypertensive agent: L-type

*Tityus serrulatus* BPP Anti-hypertensive agent [96]

inductor

*Bufo bufo gargarizans* Bufalin NaK+-ATPase inhibitor [165]

*Rana margaratae* Margaratensin Neurotensin-like peptide [164]

Scorpions *Buthus martensii* BPP Anti-hypertensive agent [97]

Toads and Frogs *Atelopus zeteki* Atelopidtoxin Hypotensive agent and ventricular fibrillation

*Rana igromaculata* Bradykinin Hypotensive agent and smooth muscle

*Rana temporaria* Bradykinin Hypotensive agent and smooth muscle

Semi-purified skin

Bees and Wasps *Apis mellifera* Cardiopep Beta-adrenergio-like stimulant and anti-

extracts

*Crotalus durissus cascavella*

*Crotalus durissus terrificus*

*Dendroaspis jamesoni*

*Dendroaspis polylepis*

*Dendroaspis angusticeps*

*kaimosae*

*polylepis*

*Pseudocerastes persicus*

*Trimeresurus flavoviridis*

*Trimeresurus stejnegeri*

*Leiurus quinquestriatus*

*spatulata*

*Pseudophryne coriacea*

Spiders *Grammostola*

### **7.4. Toxins acting on inflammatory and nociceptive responses**

Venom from the tropical ant *Pseudomyrex triplarinus* relieves pain and inflammation in rheu‐ matoid arthritis [241]. Venom from the *P. triplarinus* contains peptides called myrmexins that relieve pain and inflammation in patients with rheumatoid arthritis and inhibit inflam‐ matory carragenin-induced edema in mice [242].

### **7.5. Toxins acting on immunological system**

The most frequent cause of insect venom allergy in the Southeastern USA is the imported fire ant and the allergens are among the most potent known. Fire ant venom is a potent al‐ lergy-inducing agent containing four major allergens, Sol i I, Sol i II, Sol i III and Sol i IV [243-244].

### **7.6. Toxins with anticancer and cytotoxic activities**

Solenopsin A, a primary alkaloid from the fire ant *Solenopsis invicta*, exhibits antiangiogenic activity. Among the results obtained in this study, one of the most interesting was the selec‐ tive inhibition of Akt by solenopsin *in vitro*, that is of great interest since few Akt inhibitors have been developed, and Akt is a key molecular target in the pharmacological treatment of cancer [245]. Glycosphingolipid 7, identified in the millipede *Parafontaria laminata armigera,* suppressed cell proliferation and this effect was associated with suppression of the activa‐ tion of FAK (focal adhesion kinase), Erk (extracellular signal-regulated kinase), and Akt in melanoma B16F10 cells. Cells treated with glycosphingolipid 7 reduced the expression of the proteins responsible for the progression of cell cycle, cyclin D1 and CDK4 [246].

#### **7.7. Toxins with insecticides applications**

Peptides named ponericins from ant *Pachycondyla goeldii* have a marked action as insecti‐ cides. Among the peptides showed insecticidal activity are the ponericins G1, G2 and poner‐ icins belonging to the family W [238].

In Table 1, is presented a summary of the main biotechnological/pharmacological applica‐ tions of toxins from venomous animals covered in this chapter.


Toxins from Venomous Animals: Gene Cloning, Protein Expression and Biotechnological Applications http://dx.doi.org/10.5772/52380 43

*Candida albicans* [239]. Two antimicrobial peptides from centipede venoms, scolopin 1 and 2

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

Venom from the tropical ant *Pseudomyrex triplarinus* relieves pain and inflammation in rheu‐ matoid arthritis [241]. Venom from the *P. triplarinus* contains peptides called myrmexins that relieve pain and inflammation in patients with rheumatoid arthritis and inhibit inflam‐

The most frequent cause of insect venom allergy in the Southeastern USA is the imported fire ant and the allergens are among the most potent known. Fire ant venom is a potent al‐ lergy-inducing agent containing four major allergens, Sol i I, Sol i II, Sol i III and Sol i IV

Solenopsin A, a primary alkaloid from the fire ant *Solenopsis invicta*, exhibits antiangiogenic activity. Among the results obtained in this study, one of the most interesting was the selec‐ tive inhibition of Akt by solenopsin *in vitro*, that is of great interest since few Akt inhibitors have been developed, and Akt is a key molecular target in the pharmacological treatment of cancer [245]. Glycosphingolipid 7, identified in the millipede *Parafontaria laminata armigera,* suppressed cell proliferation and this effect was associated with suppression of the activa‐ tion of FAK (focal adhesion kinase), Erk (extracellular signal-regulated kinase), and Akt in melanoma B16F10 cells. Cells treated with glycosphingolipid 7 reduced the expression of the

Peptides named ponericins from ant *Pachycondyla goeldii* have a marked action as insecti‐ cides. Among the peptides showed insecticidal activity are the ponericins G1, G2 and poner‐

In Table 1, is presented a summary of the main biotechnological/pharmacological applica‐

**Source Toxin Application Ref.** Toxins acting on cardiovascular system

*Bothrops jararaca* BPP Anti-hypertensive agent (development of

NP Anti-hypertensive agent [21]

[16]

captopril and derivatives)

proteins responsible for the progression of cell cycle, cyclin D1 and CDK4 [246].

tions of toxins from venomous animals covered in this chapter.

were identified from venoms of *Scolopendra subspinipes mutilan* [240].

**7.4. Toxins acting on inflammatory and nociceptive responses**

matory carragenin-induced edema in mice [242].

**7.6. Toxins with anticancer and cytotoxic activities**

**7.7. Toxins with insecticides applications**

icins belonging to the family W [238].

Snakes *Agkistrodon halys*

*blomhoffii*

**7.5. Toxins acting on immunological system**

[243-244].

Applications

42



*Bothrops asper* Myotoxin II Anti-bacterial agent [50] *Bothrops jararaca* LAAO Antiparasitic agent [48]

Toxins from Venomous Animals: Gene Cloning, Protein Expression and Biotechnological Applications

[47]

45

http://dx.doi.org/10.5772/52380

agent

*Bothrops neuwiedi* Neuwiedase Antiparasitic agent [55] *Bothrops pirajai* BpirLAAO-I Anti-bacterial and antiparasitic agent [44] *Bungarus fasciatus* BFPA Anti-bacterial agent [53]

*Echis carinatus* EcTx-I Anti-bacterial agent [51] *Naja atra* Vgf-1 Anti-bacterial agent [54] *Naja naja oxiana* LAAO Anti-bacterial agent [46] *Porthidium nasutum* PnPLA2 Anti-bacterial agent [52] *Trimeresurus jerdonii* TJ-LAO Anti-bacterial agent [41]

*Pandinus imperator* Pandinin I/II Antimicrobial agent [101]

*Tityus discrepans* Bactridines Anti-bacterial agent [111]

*Bufo rubescens* Telocinobufagin Anti-bacterial agent [170]

*Leptodactylus syphax* SPXs Anti-bacterial agent [171] *Rhinella jimi* Telocinobufagin Antiparasitic agent [174]

Scorpions *Hadrurus aztecus* Hadrurin Anti-bacterial agent [110]

Spiders *Lycosa carolinensis* Lycotoxins I/II Antimicrobial agent [150]

Casca LAO Anti-bacterial agent [45]

Crotoxin Antiviral agent [56] PLA2-CB Antiviral agent [56] PLA2-IC Antiviral agent [56]]

TM-LAO Anti-bacterial agent [43]

Defensin Anti-bacterial agent [102]

Opistoporin I/II Anti-bacterial and antifungal agent [106]

Scorpine Anti-bacterial and antiparasitic agent [104]

Bufalin Antiviral agent [173] Cinobufagin Antiviral agent [173]

Marinobufagin Anti-bacterial agent [170]

Apinaceamine Anti-bacterial agent [172]

Antimicrobial agent [109]

Anti-bacterial agent [172]

*Bothrops marajoensis* BmarLAAO Anti-bacterial, antifungal and antiparasitic

*Crotalus durissus cascavella*

*Crotalus durissus terrificus*

*Trimeresurus mucrosquamatus*

*Opistophthalmus carinatus*

Toads and Frogs *Bufo bufo gargarizans* 6-methyl-

*Leptodactylus pentadactylus*

*Parabuthus schlechteri* Cationic amphipatic

peptide

spinaceamine

*Leiurus quinquestriatus*


*Vespa basalis* Mastoparan B Anti-hypertensive agent [186]

(Viprinex®)

disorders

(Defibrase®)

*Bothrops erythromelas* BE-I-PLA2 Antiplatelet agent [39]

*Echis carinatus* Echistatin Antiplatelet agent [30]

disorders

*Vespa orientalis* Protease I Anticoagulant agent [192] *Vespa magnifica* Magnifin Inductor platelet aggregation agent [193]

*Lonomia achelous* Lonomin V Inhibitor platelet aggregation agent [236]

Toxins with antibiotic activity Snakes *Bothrops alternatus* Balt-LAAO-I Anti-bacterial agent [42]

Ancrod Anticoagulant and defibrinogenating agent

Treatment of hemorrhages (Haemocoagulase®)

disorders and strokes

Trimarin Treatment and prevention of thrombotic disorders

Leucurogin Antiplatelet agent [32]

Barbourin Antiplatelet agent [31]

Prothrombin activator, thrombin-like

Prothrombin activator, thrombin-like

Prothrombin activator, thrombin-like

Bi-KTI Plasmin inhibitor agent [187]

Magnvesin Anticoagulant agent [191]

Lopap Prothrombin activator agent [233] Lonofibrase Fibrinogenolytic and fibrinolytic agent Agent [234] Losac Procoagulant agent [235]

protease and a plasmin-like protease agent [190]

protease and a plasmin-like protease agent [188]

protease and a plasmin-like protease agent [189]

[34]

[35]

[33]

[13]

[36]

[38]

[37]

Toxins acting on hemostasis

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

*Bothrops alternatus* Bhalternin Treatment and prevention of thrombotic

*Bothrops atrox* Batroxobin Anticoagulant and defibrinogenating agent

*Bothrops leucurus* BleucMP Treatment and prevention of cardiovascular

*Vipera lebetina* VLH2 Treatment and prevention of thrombotic

Spiders *Loxosceles.* Phospholipase-D Platelet aggregation inductor [149] Toads and Frogs *Bombina maxima* Bm-ANXA2 Antiplatelet agent [169]

Mixture of a TLE with a thromboplastin-like

enzyme

Bs-VSP

Bi-VSP

Snakes *Agkistrodon*

Applications

44

*rhodostoma*

*Sisturus miliaris barbouri*

*Trimeresurus malabaricus*

*sapporoensis*

*Bombus ignites*

*Lonomia obliqua*

*Bombus terrestris* Bt-VSP

Bees and Wasps *Bombus hypocrita*

Ants, Centipedes and Caterpillars


> *Leiurus quinquestriatus*

Bees and Wasps *Agelaia pallipes*

*pallipes*

*Pimpla hypochondriaca*

*Apis mellifera*

*Polistes gallicus*

*Vespa magnifica*

*Solenopsis invicta*

*Agkistrodon halys brevicaudus*

Ants, Centipedes and Caterpillars

Vesp c 1

*Orthochirus scrobiculosus* Agitoxin I/II/III K+ channel blocker [122]

http://dx.doi.org/10.5772/52380

OSK1 Immunosuppressive agent [119]

Protonectin 1-6 Chemotactic agent [211]

Api m 1 Allergen [213] Api m 2 Allergen [213] Api m 6 Allergen [206]

rVPr1 Immunosuppressive agent [210] rVPr3 Immunosuppressive agent [210]

(phospholipase A1) Allergen [207-20

Vesp c 5 (antigen-5) Allergen [207-20

Polybia-CP Chemotactic agent [212]

Vesp ma 2 Allergen agent [207-20

Vesp ma 5 Allergen [207-20

Sol i I Allergen [244] Sol i II Allergen [243] Sol i III Allergen [243] Sol i IV Allergen [243]

ACTX-6 Anticancer agent: L-amino acid oxidase [82]

Salmosin Anticancer agent: disintegrin [74]

8]

47

8]

8]

8]

*Pandinus imperator* Pi1 K+ channel blocker [125]

Toxins from Venomous Animals: Gene Cloning, Protein Expression and Biotechnological Applications

*Loxosceles reclusa* SMase D Antiserum [155]

*Polistes annularis* Pol a 5 Allergen [213]

*Polybia paulista* Polybia-MPI Chemotactic agent [212]

*Vespula germanica* Ves g 5 Allergen [213] *Vespula vulgaris* Ves v 5 Allergen [213]

*Agkistrodon contortrix* Contortrostatin Anticancer agent: disintegrin [75]

*Bothrops brazili* sPLA2 Anticancer agent [86] *Bothrops jararacussu* BJcuL Anticancer agent [89] *Bothrops leucurus* Bl-LAAO Anticancer agent [84]

Toxins with anticancer and cytotoxic activity Snakes *Agkistrodon acutus* Accutin Anticancer agent: disintegrin [73]

Spiders *Loxosceles laeta* SMase D Antiserum [155]


Toxins from Venomous Animals: Gene Cloning, Protein Expression and Biotechnological Applications http://dx.doi.org/10.5772/52380 47

Hellebrigenin Antiparasitic agent [174]

MP-VB1 Anti-bacterial and antifungal agent [198] VESP-VB1 Anti-bacterial and antifungal agent [198]

Scolopin 1 Anti-bacterial and antifungal agent [240] Scolopin 2 Anti-bacterial and antifungal agent [240]

Crotamine Antinociceptive agent [63] Crotoxin Antinociceptive agent [64] Hyal Anti-edematogenic agent [59]

J123 peptide K+ channel blocker [112]

Psalmotoxin 1 Antinociceptive and anti-inflammatory agent [151]

Dermorphins Opioid analgesic agents [61]

Melittin Anti-inflammatory agent [202] MCDP Anti-inflammatory agent [204]

Crotapotin Immunossupressive agent [69] Crotoxin Immunossupressive agent [68]

Kaliotoxin Ca2+ activated K+ channel [121]

Margatoxin Immunosuppressive agent [120]

Bees and Wasps *Apis mellifera* Melittin Anti-bacterial agent [195]

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

Toxins acting on inflammatory and nociceptive responses

Scorpions *Buthus martensii* BmKIT2 Antinociceptive agent [115]

Spiders *Loxosceles laeta* SMase D Pro-inflammatory agent [152]

Toads and Frogs *Epipedobates tricolor* Epibatidine Antinociceptive agent [175]

Toxins acting on immunological system

*Vespa bicolor*

*Scolopendra subspinipes mutilan*

*terrificus*

*Psalmopoeus cambridgei*

*Pseudomyrex*

Bees and Wasps *Apis mellifera*

Snakes *Crotalus durissus*

Scorpions *Androctonus*

*terrificus*

*mauretanicus*

*Centruroides margaritatus*

Ants, Centipedes and Caterpillars

Snakes *Crotalus durissus*

Ants, Centipedes and Caterpillars

Applications

46

*Bombus ignites* Bi-Bombolitin Anti-bacterial and antifungal agent [196] *Osmia rufa* Osmin Anti-bacterial and antifungal agent [197]

*Myrmecia pilosula* Pilosulin 1 Anti-bacterial and antifungal agent [239]

*Lachesis muta* βPLI Phospholipase inhibitor [58] *Naja atra* Cobrotoxin Antinociceptive agent [65] *Ophiophagus hannah* Hannalgesin Antinociceptive agent [66]

*Loxosceles reclusa* Phospholipase D Pro-inflammatory agent [152]

*Phyllomedusa sp* Deltorphins Opioid analgesic agents [176]

*triplarinus* Myrmexins Anti-inflammatory agent [242]

*Ophiophagus hannah* OVF Complement system activator agent [71]

*Centruroides limbatus* Hongotoxin K+ channel blocker [123]

*Centruroides noxius* Noxiustoxin K+ channel blocker [124]


Toads and Frogs *Agalychnis litodryas* Peptides from skin

*Buthus occitanus mardochei*

*Leiurus quinquestriatus*

*Leiurus quinquestriatus hebraeus*

and Caterpillars *Pachycondyla goeldii*

Ants, Centipedes

**8. Conclusion**

secretion

Bees and Wasps Wasp venom Mastoparan Stimulator of insulin secretion agent [226] Toxins with insecticides applications Scorpions *Androctonus australis* AaH IT1 Anti-insect agent [142]

> *Buthotus judaicu* Bjα IT Anti-insect agent [137] *Buthus martensii* BmKM1 Anti-insect agent [140] *Buthus martensii* Bm 32/33 Anti-insect agent [144] *Buthus occitanus* Bot IT1 Anti-insect agent [135]

> Toxins from Venomous Animals: Gene Cloning, Protein Expression and Biotechnological Applications

*Odonthobuthus doriae*OD1 Anti-insect agent [137]

*Loxosceles intermedia* LiTxx1/ LiTxx2/ LiTxx3 Anti-insect agent [158] *Paracoelotes luctuosus* δ-PaluIT1/ δ-PaluIT2 Anti-insect agent [162] *Phoneutria nigriventer* Tx4(6-1) Anti-insect agent [160]

Spiders *Loxosceles arizonica* SMase D Anti-insect agent [161]

**Table 1.** Summary of the main biotechnological/pharmacological applications of toxins from venomous animals.

The biodiversity of venoms and toxins made it a unique source of leads and structural tem‐ plates from which new therapeutic agents may be developed. Such richness can be useful to biotechnology and/or pharmacology in many ways, with the prospection of new toxins in this field. Venoms of several animal species such as snakes, scorpions, toads, frogs and their active components have shown potential biotechnological applications. Recently, using mo‐ lecular biology techniques and advanced methods of fractionation, researchers have ob‐ tained different native and/or recombinant toxins and enough material to afford deeper insight into the molecular action of these toxins. The mechanistic elucidation of toxins as well as their use as drugs will depend on insight into toxin biochemical classification, struc‐ ture/conformation determination and elucidation of toxin biological activities based on their molecular organization, in addition to their mechanism of action upon different cell models as well as their cellular receptors. Furthermore, expansions in the fields of chemistry and bi‐

Bom III/IV Anti-insect agent [139]

Lqhα IT Anti-insect agent [134]

Lqh III/ VI/ VII Anti-insect agent [141]

Ponericins G1 Insecticide Agent [238] Ponericins G2 Insecticide Agent [238] Ponericins family W Insecticide Agent [238]

Insulin-releasing activity [182]

http://dx.doi.org/10.5772/52380

49


Toxins with insulin releasing activity

Toxins from Venomous Animals: Gene Cloning, Protein Expression and Biotechnological Applications http://dx.doi.org/10.5772/52380 49


**Table 1.** Summary of the main biotechnological/pharmacological applications of toxins from venomous animals.

### **8. Conclusion**

Metalloproteinase Anticancer agent [90] Lectin Anticancer agent [91]

Rhodostomin Anticancer agent: disintegrin [78]

OHAP-1 Anticancer agent: L-amino acid oxidase [83]

Bengalin Anticancer agent [116]

Chlorotoxin Anticancer agent [126] rBmK CTa Anticancer agent [130]

Gomesin Cytotoxic and anticancer agent [157]

Psalmotoxin 1 Anticancer agent [156]

Cutaneous venom Anticancer agent [180]

Cinobufagin Anticancer agent [178]

treat immune-mediated diseases

Polybia-MPI Cytotoxic and antiproliferative agent [223]

erythrocytes) [222]

erythrocytes) [222]

[177]

*Bothrops neuwiedii* sPLA2 Anticancer agent [85]

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

*Crotalus atrox* Crotatroxin Anticancer agent: disintegrin [77] *Naja naja* Disintegrin Anticancer agent [79] *Naja naja naja* sPLA2 Anticancer agent [87] *Ophiophagus hannah* LAAO Anticancer agent [81]

*Trimeresurus jerdonii* Jerdonin Anticancer agent: disintegrin [76]

*Tityus discrepans* Neopladine 1 and 2 Anticancer agent [131]

*Bufo bufo gargarizans* Bufalin Anticancer agent [178]

*Formosan Ch'an Su* Bufotalin Anticancer agent [179] *Rana ridibunda* Brevinin-2R Anticancer agent [181]

Polybia-MP-II Cytotoxic agent (hemolytic activity on

Polybia-MP-III Cytotoxic agent (hemolytic activity on

*armigera* Glycosphingolipid 7 Anticancer agent [246] *Solenopsis invicta* Solenopsin A Anticancer agent [245]

*Venenum Bufonis* CBG Anticancer and immunotherapeutic agent to

Bees and Wasps *Lasioglossum laticeps* Lasioglossins Anticancer agent [219]

Toxins with insulin releasing activity

*Calloselasma rhodostoma*

*Trimeresurus flavoviridis*

*bengalensis*

*gomesiana*

*Psalmopoeus cambridgei*

*Polybia paulista*

*Parafontaria laminata*

Ants, Centipedes and Caterpillars

*Leiurus quinquestriatus*

Scorpions *Heterometrus*

Applications

48

Spiders *Acanthoscurria*

Toads and Frogs *Bombina variegata pachypus*

> The biodiversity of venoms and toxins made it a unique source of leads and structural tem‐ plates from which new therapeutic agents may be developed. Such richness can be useful to biotechnology and/or pharmacology in many ways, with the prospection of new toxins in this field. Venoms of several animal species such as snakes, scorpions, toads, frogs and their active components have shown potential biotechnological applications. Recently, using mo‐ lecular biology techniques and advanced methods of fractionation, researchers have ob‐ tained different native and/or recombinant toxins and enough material to afford deeper insight into the molecular action of these toxins. The mechanistic elucidation of toxins as well as their use as drugs will depend on insight into toxin biochemical classification, struc‐ ture/conformation determination and elucidation of toxin biological activities based on their molecular organization, in addition to their mechanism of action upon different cell models as well as their cellular receptors. Furthermore, expansions in the fields of chemistry and bi‐

ology have guided new drug discovery strategies to maximize the identification of biotech‐ nological relevant toxins. In fact, with so much diversity in the terrestrial fauna to be explored in the future, is extremely important providing a further stimulus to the preserva‐ tion of the precious ecosystem in order to develop the researches focusing on identify and isolate new molecules with importance in biotechnology or pharmacology.

[5] Quintero-Hernández, V., Ortiz, E., Rendón-Anaya, M., Schwartz, E. F., Becerril, B., Corzo, G., & Possani, L. D. (2011). Scorpion and spider venom peptides: Gene clon‐

Toxins from Venomous Animals: Gene Cloning, Protein Expression and Biotechnological Applications

http://dx.doi.org/10.5772/52380

51

[6] Verano-Braga, T., Rocha-Resende, C., Silva, D. M., Ianzer, D., Martin-Eauclaire, M. F., Bougis, P. E., De Lima, ME, Santos, R. A. S., & Pimenta, A. M. C. (2008). Tityus serru‐ latus Hypotensins: A new family of peptides from scorpion venom. *Biochemical and*

[7] Almeida, D. D., Scortecci, K. C., Kobashi, L. S., Agnez-Lima, L. F., Medeiros, S. R. B., Silva-Junior, A. A., Junqueira-de-Azevedo, I. L. M., & Fernandes-Pedrosa, M. F. (2012). Profiling the resting venom gland of the scorpion Tityus stigmurus through a

[8] Petricevich, V. L. (2010). Scorpion venom and the inflammatory response. *Mediators*

[9] Tambourgi, D. V., Pedrosa, M. F. F., Van Den, Berg. C. W., Gonçalves-de-Andrade, R. M., Ferracini, M., Paixão-Cavalcante, D., Morgan, B. P., & Rushmere, N. K. (2004). Molecular cloning, expression, function and immunoreactivities of members of a gene family of sphingomyelinases from Loxosceles venom glands. *Molecular Immu‐*

[10] Senff-Ribeiro, A., Henrique, da., Silva, P., Chaim, O. M., Gremski, L. H., Paludo, K. S., Bertoni da. Silveira, R., Gremski, W., Mangili, O. C., & Veiga, S. S. (2008). Biotech‐ nological applications of brown spider (Loxosceles genus) venom toxins. *Biotechnolo‐*

[11] Habermehl, GG. (1995). Antimicrobial activity of amphibian venoms. *Studies in Natu‐*

[13] Sajevic, T., Leonardi, A., & Križaj, I. (2011). Haemostatically active proteins in snake

[14] Koh, C. Y., & Kini, R. M. (2012). From snake venom toxins to therapeutics- cardiovas‐

[15] Hodgson, W. C., & Isbister, G. K. (2009). The application of toxins and venoms to car‐ diovascular drug discovery. *Current Opinion in Pharmacology*, 9(2), 173-176.

[16] Ferreira, S. H. (1965). A bradykinin-potentiating factor (BPF) present in the venom of Bothrops jararaca. *British Journal of Pharmacology and Chemotherapy*, 24(1), 163-169. [17] Barreto, S. A., Chaguri, L. C. A. G., Prezoto, B. C., & Lebrun, I. (2012). Characteriza‐ tion of two vasoactive peptides isolated from the plasma of the snake Crotalus duris‐

[18] Vink, S., Jin, A. H., Poth, K. J., Head, G. A., & Alewood, P. F. (2012). Natriuretic pep‐

[12] Habermann, E. (1972). Bee and wasp venoms. *Science*, 177(4046), 314-322.

sus terrificus. Biomedicine and Pharmacotherapy , 66(4), 256-265.

tide drug leads from snake venom. *Toxicon*, 59(4), 434-445.

ing and peptide expression. *Toxicon*, 58(8), 644-663.

*Biophysical Research Communications*, 371(3), 515-520.

transcriptomic survey. *BMC Genomics*, 13, 362.

*of Inflammation*, 903295.

*nology*, 41(8), 831-840.

*gy Advances*, 26(3), 210-218.

*ral Products Chemistry, Part C*, 327-339.

cular examples. *Toxicon*, 59(4), 497-506.

venoms. *Toxicon*, 57(5), 627-645.
