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Instant insight: Venomous drugs?
15 December 2006
Elba Villegas and Gerardo Corzo, biotechnology researchers at the Universidad Autonoma del Estado de Morelos and the Universidad Nacional Autonoma de Mexico, set the record straight about spiders.
Spiders are nature's pest controllers. These eight-legged, web-forming arachnid predators are equipped with two venom glands full of valuable chemicals designed to kill insect prey. Such compounds, from small organic molecules to complex structures such as acylpolyamines, neuropeptides and enzymes, are precious ligands that target several biological receptors. Since insect receptors are not substantially different from those of humans and other mammals, the majority of the molecules contained in spider venom could also target human receptors.
The potential medical uses of spider venoms are largely due to their selectivity and affinity for ion channels.
The potential medical uses of spider venoms are largely due to their selectivity and affinity for ion channels [proteins that allow ions to cross cell membranes] and other receptors. This makes them suitable for studying cell function and for designing therapeutic drugs. As an example, the venom of the theraphosid Grammostola spatulata from South America contains a peptide, GsMtx-4, that blocks stretch-activated ion channels. These channels are sensitive to muscle contraction and blood pressure and play an important role in coordinating a heartbeat. Potentially, GsMtx-4 could be used to prevent atrial fibrillation after a heart attack and to treat cardiac patients.
A special group of the spider peptides have a mixed hydrophilic-hydrophobic nature - they are amphipathic. These form -helical structures that insert into cell membranes to form pores, resulting in loss of cell function. Although most of these peptides will destroy red blood cells, they could potentially be used in topical applications, such as antibacterial coatings for medical implants, in inhibiting the growth of oral bacteria associated with tooth decay and early plaque formation and in treating skin infections.
Venom peptides contain a common basic structure called a 'cysteine knot,' a tangle of protein chains and disulfide bridges that gives them an excellent molecular stability. Also, the small organic components of spider venom, such as organic acids, amines, nucleic acids and amino acids, are thought to stabilise the mixture and enhance the delivery and effectiveness of the peptides.
Finally, enzymes and large protein components of spider venoms are of special medical importance. For example, the neurotoxic protein -latrotoxin, from the black widow spider, causes massive neurotransmitter release. Similarly, an active enzyme in the venom of the brown recluse spider is sphingomyelinase D, which degrades cell membranes and causes painful lesions to develop. Another component of brown recluse spider venom, hyaluronidase, belongs to a family of compounds that have shown medical potential as tumour treatments.
Read Elba Villegas and Gerardo Corzo's review 'Spider venoms: A rich source of acylpolyamines and peptides as new leads for CNS drugs' in February's issue of Natural Product Reports.
Spider venoms: a rich source of acylpolyamines and peptides as new leads for CNS drugs
G Estrada, E Villegas and G Corzo, Nat. Prod. Rep., 2007,