Pharmacologically active spider peptide toxins

Abstract

Advances in mass spectrometry and peptide biochemistry coupled to modern methods in electrophysiology have permitted the isolation and identification of numerous novel peptide toxins from animal venoms in recent years. These advances have also opened up the field of spider venom research, previously unexplored due to methodological limitations. Many peptide toxins from spider venoms share structural features, amino acid composition and consensus sequences that allow them to interact with related classes of cellular receptors. They have become increasingly useful agents for the study of voltage-sensitive and ligand-gated ion channels and the discrimination of their cellular subtypes. Spider peptide toxins have also been recognized as useful agents for their antimicrobial properties and the study of pore formation in cell membranes. Spider peptide toxins with nanomolar affinities for their receptors are thus promising pharmacological tools for understanding the physiological role of ion channels and as leads for the development of novel therapeutic agents and strategies for ion channel-related diseases. Their high insecticidal potency can also make them useful probes for the discovery of novel insecticide targets in the insect nervous system or for the development of genetically engineered microbial pesticides.

Differential contribution of Kv4-containing channels to A-type, voltage-gated potassium currents in somatic and visceral dorsal root ganglion neurons

“…These toxins act on a nonpore region to exhibit voltagedependent inhibition of target channel currents (Corzo and Escoubas 2003;Norton and Pallaghy 1998;Swartz 2007;Zarayskiy et al 2005). With the use of heterologously expressed Kv4.x currents, we found that PaTx2 shows distinct voltage dependencies for their inhibition.…”

Biochemical and pharmacological study of venom of the wolf spider Lycosa singoriensis

“…Spider venoms are complex chemical cocktails in which peptides are the principal constituents of most spider venoms, except those of black widow spiders that contain a high proportion, greater than 100 kD proteins (1)(2)(3). The spider venom peptides are produced in a combinatorial fashion, which leads to an estimated total of about 1.5 million spider venom peptides.…”

Stichodactyla helianthusPeptide, a Pharmacological Tool for Studying Kv3.2 Channels

“…Kv channels are tetrameric structures formed by the association of identical or closely related subunits. The study of potassium channels has been greatly facilitated by the discovery of high-affinity and selective channel inhibitors in the venoms of different organisms (Garcia et al, 1998;Corzo and Escoubas, 2003;Lewis and Garcia, 2003). Such peptidyl inhibitors have provided invaluable pharmacological tools for the isolation, purification, tissue localization, and the study of the structure and gating mechanism of ion channels (Garcia-Calvo et al, 1994).…”