Abstract
Spiders are the most successful venomous animals and the most abundant terrestrial predators. Their remarkable success is due in large part to their ingenious exploitation of silk and the evolution of pharmacologically complex venoms that ensure rapid subjugation of prey. Most spider venoms are dominated by disulfide-rich peptides that typically have high affinity and specificity for particular subtypes of ion channels and receptors. Spider venoms are conservatively predicted to contain more than 10 million bioactive peptides, making them a valuable resource for drug discovery. Here we review the structure and pharmacology of spider-venom peptides that are being used as leads for the development of therapeutics against a wide range of pathophysiological conditions including cardiovascular disorders, chronic pain, inflammation, and erectile dysfunction.
Highlights
IntroductionSpiders are the most successful venomous animals with an estimated 100,000 extant species [1]
The Diverse Pharmacology of Spider VenomsSpiders are the most successful venomous animals with an estimated 100,000 extant species [1].The vast majority of spiders employ a lethal cocktail to rapidly subdue their prey, which are often many times their own size
U1-TRTX-Pc1a (Psalmopeotoxin I) and U2-TRTX-Pc1a (Psalmopeotoxin II) are inhibitor cystine knot (ICK) peptides isolated from the venom of the Trinidad chevron tarantula Psalmopoeus cambridgei that are effective against the intra-erythrocyte stage of Plasmodium falciparum
Summary
Spiders are the most successful venomous animals with an estimated 100,000 extant species [1]. The crude venom of Macrothele raveni has antitumor activity, for which the responsible component has not yet been identified [22,23] Larger toxins such as the latrotoxins from the infamous black widow spider (Latrodectus mactans) and related species induce neurotransmitter release and they have played an important role in dissecting the process of synaptic vesicle exocytosis [24]. Since spiders employ their venom primarily to paralyse prey, it is no surprise that these venoms contain an abundance of peptides that modulate the activity of neuronal ion channels and receptors. In this review we examine the structure, targets, and mechanisms of action of spider-venom peptides with potential therapeutic applications
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