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Animal venom studies: Current benefits and future developments

World Journal of Biological Chemistry 2015年第2期6卷 28-33页

作者： Yuri N Utkin laboratory of molecular toxinology ShemyakinOvchinnikov Institute of Bioorganic Chemistry

Poisonous organisms are represented in many taxa, including kingdom Animalia. During evolution, animals have developed special organs for production and injection of venoms. Animal venoms are complex mixtures, compositions of which depend on species producing venom. The most known and studied poisonous terrestrial animals are snakes, scorpions and spiders. Among marine animals, these are jellyfishes, anemones and cone snails. The toxic substances in the venom ofthese animals are mainly of protein and peptide origin. Recent studies have indicated that the single venom may contain up to several hundred different components producing diverse physiological effects. Bites or stings by certain poisonous species result in severe envenomations leading in some cases to death. This raises the problem of bite treatment. The most effective treatment so far is the application of antivenoms. To enhance the effectiveness of such treatments, the knowledge of venom composition is needed. On the other hand, venoms contain substances with unique biological properties, which can be used both in basic science and in clinical applications. The best example of toxin application in basic science is α-bungarotoxin the discovery of which made a big impact on the studies of nicotinic acetylcholine receptor. Today compositions of venom from many species have already been examined. Based on these data, one can conclude that venoms contain a large number of individual components belonging to a limited number of structural types. Often minor changes in the amino acid sequence give rise to new biological properties. Change in the living conditions of poisonous animals lead to alterations in the composition of venoms resulting in appearance of new toxins. At the same time introduction of new methods of proteomics and genomics lead to discoveries of new compounds, which may serve as research tools or as templates for the development of novel drugs. The application of these sensitive and comprehensiv

关键词： Venom Poison Snake Scorpion Spider Toxin

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Last decade update for three-finger toxins: Newly emerging structures and biological activities

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World Journal of Biological Chemistry 2019年第1期10卷 17-27页

作者： Yuri N Utkin laboratory of molecular toxinology Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry

Three-finger toxins(TFTs) comprise one of largest families of snake venom toxins. While they are principal to and the most toxic components of the venoms of the Elapidae snake family, their presence has also been detected in the venoms of snakes from other families. The first TFT, α-bungarotoxin, was discovered almost 50 years ago and has since been used widely as a specific marker of the α7 and muscle-type nicotinic acetylcholine receptors. To date, the number of TFT amino acid sequences deposited in the UniProt Knowledgebase free-access database is more than 700, and new members are being added *** structural variations among the TFTs are not numerous, several new structures have been discovered recently; these include the disulfide-bound dimers of TFTs and toxins with nonstandard pairing of disulfide bonds. New types of biological activities have also been demonstrated for the well-known TFTs, and research on this topic has become a hot topic of TFT studies. The classic TFTs α-bungarotoxin and α-cobratoxin, for example, have now been shown to inhibit ionotropic receptors of γ-aminobutyric acid, and some muscarinic toxins have been shown to interact with adrenoceptors. New, unexpected activities have been demonstrated for some TFTs as well, such as toxin interaction with interleukin or insulin receptors and even TFT-activated motility of sperm. This minireview provides a summarization of the data that has emerged in the last decade on the TFTs and their activities.

关键词： Three-finger toxins Snake Venom Structure Biological activity

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Study of Free-Radical Processes during Rotenone Modeling of Parkinson Disease

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Journal of Biophysical Chemistry 2016年第1期7卷 1-8页

作者： Narine A. Ghazaryan Lusine A. Ghulikyan Vergine A. Chavushyan Naira M. Ayvazyan L.A. Orbeli Institute of Physiology NAS RA Laboratory of Toxinology and Molecular Systematics Yerevan Armenia

The study has shown free radical processes during modeling of Parkinson Disease (PD) with rotenone. We isolated striatum, brainstem, neocortex, cerebellum, spinal cord, thymus, heart, and liver of rats after rotenone injection in the right striatum. The samples were taken on the 5th, 10th and 15th days after the injection. According to chemiluminescence data, the injection of rotenone initiates the disturbance of intensity of free radical processes in striatum at 5th day in a bilateral mode. After this until the 10th day these changes had restoring character, but after 15 days according to chemiluminescence and thio-barbituric acid test disturbance of lipid peroxide oxidation processes occurred. While superoxide dismutase activity has been changed significantly in all studied tissues, especially in the striatum and neocortex. It should be noted that during rotenone model there are no observed clinical symptoms in rats during 1 to 20 days, and the symptoms of the disease are observed approximately 28 days after the injection. This research could help diagnose PD in the early stage of its onset.

关键词： Parkinson’s Disease Rotenone Chemiluminescence Thio-Barbituric Acid Test Superoxide Dismutase Activity

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Modern trends in animal venom research-omics and nanomaterials

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World Journal of Biological Chemistry 2017年第1期8卷 4-12页

作者： Yuri N Utkin laboratory of molecular toxinology ShemyakinOvchinnikov Institute of Bioorganic Chemistry117997 MoscowRussia National University of Science and Technology MISiS 119049 MoscowRussia

Animal venom research is a specialized investigation field, in which a number of different methods are used and this array is constantly expanding. Thus, recently emerged omics and nanotechnologies have already been successfully applied to venom research. Animal venoms have been studied for quite a long time. The traditional reductionist approach has been to isolate individual toxins and then study their structure and function. Unfortunately, the characterization of the venom as a whole system and its multiple effects on an entire organism were not possible until recent times. The development of new methods in mass spectrometry and sequencing have allowed such characterizations of venom, encompassing the identification of new toxins present in venoms at extremely low concentrations to changes in metabolism of prey organisms after envenomation. In particular, this type of comprehensive research has become possible due to the development of the various omics technologies: Proteomics, peptidomics, transcriptomics, genomics and metabolomics. As in other research fields, these omics technologies ushered in a revolution for venom studies, which is now entering the era of big data. Nanotechnology is a very new branch of technology and developing at an extremely rapid pace. It has found application in many spheres and has not bypassed the venom studies. Nanomaterials are quite promising in medicine, and most studies combining venoms and nanomaterials are dedicated to medical applications. Conjugates of nanoparticles with venom components have been proposed for use as drugs or diagnostics. For example, nanoparticles conjugated with chlorotoxin- a toxin in scorpion venom, which has been shown to bind specifically to glioma cells- are considered as potential glioma-targeted drugs, and conjugates of neurotoxins with fluorescent semiconductor nanoparticles or quantum dots may be used to detect endogenous targets expressed in live cells. The data on application of omics and nanot

关键词： Animal venom Proteomics Peptidomics Transcriptomics Nanotechnology Genomics Quantum dots Nanoparticles Metabolomics

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An overview of the marine natural products in clinical trials and on the market

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Journal of Coastal Life Medicine 2015年第6期 421-428页

作者： Marisa Rangel Miriam Falkenberg Immunopathology laboratory Division of Scientific DevelopmentButantan Institute05503-900Sao PauloBrazil laboratory of toxinology Department of Physiological SciencesUniversity of Brasilia70910-900BrasiliaDFBrazil Department of Pharmaceutical Sciences Federal University of Santa Catarina88040-970FlorianopolisSCBrazil

The first marine natural products that served as leads or scaffolds for medicines were discovered in the middle of last century:the arabinosyl glycosides from the marine sponge Tectitethya *** and modifications of the natural molecules generated antiviral and antileukemic drugs developed in the 1970’s and in the following decades,including the first effective treatment against HIV *** the improvement of techniques for the elucidation of chemical structure of the molecules,as well as chemical synthesis,especially from the 1990’s,there was an increase in the number of bioactive natural products characterized from marine *** chemical structures with high specificity towards molecular targets in cells allowed the development of new drugs with indication for the treatment of several illnesses,from cancer to new antibiotics,and even neurological *** there are at least 13 molecules derived from marine natural products on advanced clinical trials,and nine were approved to be used as *** that in the past eight years,more than 1000 new compounds from marine organisms were described,per year,the expectation is that many more drugs will be derived from marine natural products in a near future.

关键词： Marine natural products Marine drugs Anticancer drugs Antiviral drugs Analgesic drugs Clinical trials

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