At a time when I never thought I would hear another word about ACV1, I heard today from my son that scientists at the University of Queensland have engineered an orally available version by splicing together the ends of the ACV1 molecule making it a cyclic. Apparently it does better surviving the gut.
It's being pumped as a potential pain drug, as per this quote:
"Now, scientists in Australia have managed to engineer a conotoxin that can be taken orally. Researchers led by David J. Craik of the Institute for Molecular Bioscience at the University of Queensland discovered that by linking the N-terminus of α-conotoxin Vc1.1a compound derived from Conus victoriaeto its C-terminus, they could make the 16-residue peptide orally active (Angew. Chem. Int. Ed., DOI: 10.1002/anie.201000620).
"In the cyclized peptide, which is known as α-conotoxin cVc1.1, the proteins head and tail are tethered by a string of six amino acidstwo alanines flanked on each side by two glycines. Craik says he chose the linker because it was inexpensive, wouldnt add any functionality to the molecule, and would be easy to characterize with nuclear magnetic resonance. In tests with rats, the cyclized peptide proved to be as potent a painkiller as gabapentin, the most popular drug for neuropathic pain, even though the conotoxin-based peptide was administered at a dose that is less than 1% of the dose typically given for gabapentin."
Here's the link:
http://pubs.acs.org/cen/science/88/8830sci2.html
These guys apparently have never received the word that the problem with ACV1 wasn't that it isn't orally active, but that it just did not work on humans. It doesn't bind to the specific human nicotinic acetylcholine receptors that it does in almost all other species. So, you can make it as orally active as you want and it still won't cut pain.
In any case Metabolic long ago relinquished rights to the compound, so if anyone else can get it to work, it isn't going to bring anything to CZD but possible regrets.
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