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Bioprospection and chemical/functional characterization of the low molecular mass compounds from the venoms of the social wasps: Agelaia pallipes pallipes, Agelaia vicina and Polybia paulista (Hymenoptera - Vespidae)

Grant number: 06/01157-7
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): August 01, 2006
Effective date (End): December 31, 2009
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal researcher:Mario Sergio Palma
Grantee:Daniel Menezes Saidemberg
Home Institution: Instituto de Biociências (IB). Universidade Estadual Paulista (UNESP). Campus de Rio Claro. Rio Claro , SP, Brazil


Spiders and wasps constitute a large group of Arthropods present in the most of ecosystems of earth, since the deserts to the wet darkness of the rain forests, since the beaches to the heights of the mountains. The toxic secretions of many spiders and wasps were demonstrated to paralyze their insect-prey by blocking the process of glutamatergic synaptic transmission at the prey’s neuromuscular junctions (PALMA et al., 1998). Accordingly, considerable research efforts have been mounted to isolate and identify neuroactive compounds in these secretions, resulting in the discovery of many peptides and small molecules which block glutamate receptors and/or calcium channels (KOBAYASHI et al., 1992). Thus, the secretion of many of these animals proved to be useful tools for physiological studies of neuronal function, and several of the neurotoxic compounds produced by their defensive/aggressive secretions may become structural models for the rational development of neuroprotective agents for different neurological disorders. Peptides in general are not suitable as drug candidates for central nervous system disorders, due to: their susceptibility to proteolysis, possible antigenicity and their lack of penetrability to blood-brain barrier. Thus, the small organic molecule occurring in these secretions seems to be natural candidates to be mined in the search for leader compounds for development of neurotherapeutical medicine drugs. These compounds generally are very potent and selective for specific type of neuroreceptors/ ion channels. Thus, the most of them occur at sub-picomole levels, requiring highly qualified expertise staff for purification and structure elucidation of these compounds by using microanalytical techniques. The neuroassays are generally performed by using synthetic which in turn requires expertise and organic synthesis facility. To avoid the demand of large amounts (grams) of animal biomass (which the most of times is impossible to be obtained) it is necessary to use top level sophisticated spectroscopy instrumentation. When taken into account, all these requirements limited the number of research groups all over the world, involved with this type of scientific investigations at academic level. We have been involved with the structural elucidation of about 14 new structures of acylpolyamine toxins from the orb-web-spider Nephilengys cruentata, presenting non-competitive blocking activity toward NMDA-sub type of glutamate receptors. Our laboratory is also dealing with the structural elucidation of organometallic azides from the web of the spider Nephila clavipes, presenting potent insecticide activities; alkaloids like tetrahydro-b-carbolines, presenting selective insecticide activity and blocking action against benzodiazepine receptors, have been isolated and had their structures elucidated by our group from the hunting secretion of the spider Parawixia bistriata. All these investigations have been individually financed by FAPESP since 1996, and if properly supported by a research grants through a thematic project under the BIOTA - Prospection Program, these type of compounds surely will constitute a vast source of drug leads for various neurological disorders and selective pesticides. Experimental focus:-from wasps it will be focused the secretions of the defensive/aggressive glands looking for low molecular weight neurotoxic / neuroprotective and insecticide compounds ;-the insecticide effect will assayed in the laboratory by using honeybees as model insects;-neurotoxicity and neuroprotection will be assayed by using rat brain as models, with the use immunohistochemistry protocols to map the brain position of toxin action and electrophysiology to investigate the mechanisms of action. (AU)

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