Pharmacologically Active Toxins: Chronic Pain and Multiple Sclerosis
K Khoo, BJ Smith, RS Norton (Structural Biology), in collaboration with G Bulaj, BM Olivera, D Yoshikami (University of Utah), MW Pennington (Bachem Biosciences) and KG Chandy (University of California, Irvine) [Khoo KK, Feng Z-F, Smith BJ, Zhang M-M, Yoshikami D, Olivera BM, Bulaj G & Norton RS (2009) Structure of the analgesic μ-conotoxin KIIIA and effects on structure and function of disulfide deletion. Biochemistry; 213. Beeton C, Smith BJ, Sabo JK, Crossley G, Nugent D, Khaytin I, Chi V, Chandy KG, Pennington MW & Norton RS (2008) The D-diastereomer of ShK toxin selectively blocks voltage-gated K+ channels and inhibits T lymphocyte proliferation. Journal of Biological Chemistry 283, 988-997]
Venomous creatures produce a wealth of interesting peptide and protein toxins as components of their venoms. Many of these toxins are potent and highly selective blockers or modulators of ion channel function, and as such are valuable pharmacological tools, as well as being potentially useful leads in the development of new human therapeutics. We focus on peptide and protein toxins that block or modulate the activity of sodium or potassium channels. The sodium channel blockers have potential applications as new analgesics against chronic (neuropathic) pain, while the potassium channel blockers are effective in ameliorating multiple sclerosis symptoms in animal models of this debilitating disease.
