**5. Concluding remarks**

Nature has been finding ways to gift living beings with functions that are advantageous, regarding natural selection, mainly by evolutionary process. Among all the lepidopterans of


of cell interaction [104-110]. The high identity among Losac and hemolins suggests that Losac could also assume some of these functions in *L. obliqua*. The adhesive properties of Losac probably are relevant to understanding the human umbilical vein endothelial cell responses

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

Studies on *L. obliqua* toxins with a molecular approach have applications beyond the patho‐ physiology and therapeutic perspectives of envenoming. As procoagulant proteins, Lopap and Losac can be useful as tools for developing clotting assays and diagnostic kits. Exogenous factor X activators, such as recombinant Losac, has also the potential to be used for detection of factor X deficiency and lupus anticoagulant [111]. In the case of Lopap, an exogenous prothrombin activator, two patents were applied to use this compound in diagnostic kits for detection of dysprothrombinemias using the native form purified from the venom as well as the recombinant form produced in bacteria. This prothrombin activator has also the potential to be used in clotting time assays, prothrombin assays, and to monitor patients anticoagulated with hirudin. A recent study suggests that exogenous procoagulant proteins could also be considered for therapeutic use to manage bleeding complications caused by anticoagulation therapy. Treatment with Lopap was able to reduce the bleeding time of rabbits anticoagulated with low molecular weight heparin, through direct prothrombin activation, bypassing factor Xa inhibition [112]. Patent information about those applications can be consulted in Table 3. Modulation of cell responses triggered by *Lonomia* toxins can have valuable therapeutic and biotechnological applications. Promoting cell survival can be useful to improve cell culture technologies and vaccine productions, and for treatment of degenerative diseases. In addition, the effects of Lopap on extracellular matrix remodeling can be valuable to develop wound healing formulations and to regeneration issues (Table 3). For this approaches, design and synthesis of short peptides derived from Lopap amino acid sequence is an interesting task to minimize toxic and side effects and for production of this molecules for proofs of concepts, pre-clinical and clinical tests (Table 3). Isolating specific domains and sequences can also help to understand the multifunctional properties of the studied proteins and direct structure-

Unveiling the mechanisms of action and structure-function relationship of these multifunc‐ tional molecules may pointing out these molecules as promising candidates to development of new therapeutic drugs, reagents in diagnostic kits for coagulation dysfunctions, and

Nature has been finding ways to gift living beings with functions that are advantageous, regarding natural selection, mainly by evolutionary process. Among all the lepidopterans of

observed in previous studies.

Applications

196

**4. Biomedical applications**

function insights.

biotechnological applications.

**5. Concluding remarks**

**Table 3.** International patents associated to Lopap and peptides derived from its amino acid sequence. Information was obtained from World Intellectual Property Organization (WIPO).

medical interest in the world, *Lonomia* sp. caterpillars (family: Saturniidae) is the only genus that causes dramatic damages in human blood coagulation [16, 113]. This feature is reflected in the diversity of toxins produced by the caterpillar and their unusual enzymatic properties.

Application of molecular approaches in the study of *L. obliqua* toxins has been a valuable strategy in understanding the biological means of these molecules for the source organism itself and the dynamic pathways in envenoming syndrome. On the other hand, this approach reveals these toxins as interesting tools for therapeutic and biotechnological applications. The best examples are Lopap (a prothromin activator lipocalin) and Losac (the only hemolin with proteolytic activity). If, in one hand, the molecular basis of target recognition and proteolysis of factor X and prothrombin by Losac and Lopap, respectively, needs to be further investigated, on the other hand, efforts need to be focused on understanding the pro-survival activity of both molecules.

Integrating transcriptomic, proteomic and microarray analysis will provide a wealth of valuable information about venom composition. Molecular cloning and expression of re‐ combinant toxins from *L. obliqua* opens new perspectives in the identification and characteri‐ zation of macromolecular fine structure of toxins and its implications for toxic activity as well as new action mechanisms and target cell binding that should be an area of rapid development. The next several years will likely see some very significant advances in this field and, in the future, those approaches will permit the identification of molecular mechanisms at a new level.

[6] Zannin, M., et al., Blood coagulation and fibrinolytic factors in 105 patients with hemorrhagic syndrome caused by accidental contact with Lonomia obliqua caterpil‐

Toxins from *Lonomia obliqua* — Recombinant Production and Molecular Approach

http://dx.doi.org/10.5772/53697

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[8] Goncalves, L.R., et al., Efficacy of serum therapy on the treatment of rats experimen‐ tally envenomed by bristle extract of the caterpillar Lonomia obliqua: comparison

[9] Ricci-Silva, M.E., et al., Immunochemical and proteomic technologies as tools for un‐ ravelling toxins involved in envenoming by accidental contact with Lonomia obliqua

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[11] Duarte, A.C., et al., Insuficiência renal aguda por acidentes com lagartas. Journal Bra‐

[12] Kelen, E.M.A., Z.P. Picarelli, and A.C. Duarte, Hemorrhagic syndrome induced by contact with caterpillars of the genus Lonomia (saturniidae, hemileucinae). Journal of

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