Polyamines spiders/wasps

Among all the polyamine toxins, PhTX-433 has been most extensively used as template for stracture-activity relationship (SAR) studies, pioneered by the work of Nakanishi and coworkers, as described later (Strpmgaard et al. 2005 Andersen et al. 2006 Olsen et al. 2011). More recently, the structure of PhTX-433 and spider polyamine toxin NPTX-622B (17 Fig. 17.1) was combined in a spider-wasp hybrid analogue (18 Fig. 17.1) (Olsen et al. 2007). 

It is of particular interest that polyamines closely related to CNS 2103 have been found not only in other spider species (29) but also in the venom of the solitary digger wasp Philanthus triangulum (32). The similarity of these wasp and spider neurotoxins provides a notable example of convergence in the evolution of secondary metabolites aimed at a common target. 

Polyamine toxins from spiders and wasps. In The Alkaloids, vol. 45, eds. G. Cordell and A. Brossi, pp. 1-125. New York Academic Press. 

A. L. Mueller R. Roeloffs H. Jackson, Pharmacology of Polyamine Toxins from Spiders and Wasps. In Alkaloids (San Diego), G. A. Cordell, Ed. Academic Press San Diego, CA, London, 1995 Vol. 46, pp 63-94. 

C23H41N5O3, Mr 435.61. The toxin of the solitary wasp Philanthus triangulum acts as a potent, non-competitive glutamate receptor antagonist (neurotoxic effect on prey insects, e. g., grasshoppers). The main component is the polyamine P., which closely resembles the polyamines occurring in spider venoms. 

Some of the properties that would be required of a polyamine amide insecticide are an ability to gain entry into pest insects, resistance to metabolic degradation within these insects, and high potency at its site of action. There are, of course, other equally important considerations, such as persistence in the environment, cost of production, toxicity to man and other non-pest animals, and the impact on the ecosystem of the use of analogues of wasp and spider toxins as insecticides. 

The continuing interest in the polyamine amides as lead structures comes at a time of major changes in the insecticide industry, not least of which is a reappraisal of the so-called rational approach towards insecticide discovery. This may slow industrial research on these compounds. Also, developments involving natural products as starting points are being examined very critically by environmentalists and the polyamine amide toxins have not escap their attention. It has been suggested that the use of polyamine amide insecticides could lead to resistance to the natural products present in the venoms of spider and wasp. However, the potential consequences of this for the ecosystem in general are difficult to identify, let alone to estimate. 

Fig. 5 Naturally occurring spider (17-25) and wasp (26) toxins containing polyamine backbones. Many analogs of nephilatoxin-643 (NPTX-643) (24), philanthotoxin-433 (PhTX-433) (26) have been generated using solid phase chemistry (see Sect. 3)...

Keywords Ionotropic glutamate receptors Natural products Nicotinic acetylcholine receptors Polyamine toxin Solid-phase synthesis Spider and wasp... 

Chemical Synthesis of Spider and Wasp Polyamine Toxins... 

In addition to the recent studies of spider polyamine toxins, the wasp toxin PhTX-433 has also been used as a template in attempts to develop more potent and selective compounds. As described next in relationship to nACh receptors, Nakanishi and colleagues have contributed signihcantly to this area. Recently, a number of PhTX-433 have been designed, synthesized, and evaluated for inhibitory potency, in particular at AMPA receptors, leading in several cases to fairly potent and AMPA receptor selective analogues (Frplund et al. 2010 Kromann et al. 2002). 

Mueller AL, Roeloffs R, Jackson H (1995) Pharmacology of polyamine toxins from spiders and wasps. In Cordell GA (ed) The alkaloids chemistry and pheumacology, vol 46. Academic... 

Saito M, Kawai N, Miwa A, Pan-Hou H, Yoshioka M (1985) Spider toxin (JSTX) blocks glutamate synapse in hippocampal pyramidal neurons. Brain Res 346 397-399 Schafer A, Benz H, Fiedler W, Guggisberg A, Bienz S, Hesse M (1994) Polyamine toxins from spiders and wasps. In Cordell GA, Brossi A (eds) The alkaloids chemistry and pharmacology,... 

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