Toxineering: New Tool for Harnessing the Power of Nature’s Poisons | Pain Research Forum

Toxineering: New Tool for Harnessing the Power of Nature’s Poisons | Pain Research Forum

“Although spiders, snakes, and other poisonous predators get a bad rap, the diverse and highly specific peptides found in their venoms have proven quite useful for uncovering the function of ion channels and developing drugs that target them. ”

“Using this approach, termed “toxineering,” the researchers identified a tarantula spider peptide, protoxin-I, as the first high-affinity peptide antagonist of the transient receptor potential ankyrin 1 (TRPA1) channel. ”

“Predator-derived peptide toxins have long been used to elucidate the structure and function of ion channels, including in pain pathways (see PRF related news story and PRF news story). The cone snail toxin-derived N-type calcium channel blocker ziconotide is FDA approved for the treatment of intractable pain.

Among pain-transducing channels, TRPA1 plays a special role in chronic inflammatory pain, itch, and peripheral neuropathies, making it a promising potential therapeutic target (for a recent review, see Brederson et al., 2013).”

“In the current paper, Nitabach and colleagues capitalized on a 2004 discovery that naturally occurring soluble toxin peptides can be fused to membrane-bound proteins without a loss of function (Ibañez-Tallon et al., 2004)”

“Toxineering eliminates the need for venom and does not require in vitro protein folding reactions to ensure synthetic toxin bioactivity. In addition, although still in the early stages, the approach could in theory be significantly scaled up.”

“The purpose of natural toxins is to stun and immobilize prey, so they are therefore non-specific by design—a problem for drug discovery. “To take those toxins and turn them into medications, what we need to do is identify a toxin that binds and then optimize it so that it is specific for only the receptor of interest. Toxineering does both,” said Goldstein.”


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  1. Pingback: Ziconotide for Chronic Severe Pain | EDS Info (Ehlers-Danlos Syndrome)

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