Accelerating the discovery of drugs from venoms
|Professor Paul Alewood|
8 May 2009
A new method developed to identify and characterise individual molecules in the venom of animals such as the cone snail has the potential to accelerate the discovery of life-saving drugs.
A team from The University of Queensland’s Institute for Molecular Bioscience (IMB) and Rockefeller University in New York have devised the method, which will speed up the sequencing of mini-proteins known as peptides and allow them to be screened for medical uses.
Cysteine-containing peptide toxins in the venom of animals such as cone snails, snakes, spiders and scorpions have attracted interest from scientists because of their potential to target receptors on the surface of cells, which in turns allows them to perform a variety of functions including relieving pain and treating heart failure.
“Until now, the rate of discovery of new peptides has been very slow,” Professor Paul Alewood from the IMB said. “It could take a year to isolate and characterise a useful peptide given the huge number of distinct peptides in animal venoms.
“Cone snails alone are estimated to produce more than 50,000 distinct venom peptides, so it really was like searching for a needle in a haystack. However, with our new method, we were able to determine the full sequence of amino acids in 31 toxins (peptides) from a small quantity of the venom of an individual cone snail.”
The cone snail targeted was the carnivorous species Conus textile, known as ‘cloth of gold’ because of its brilliant shell. The team used the relatively new technique of electron transfer dissociation (ETD) mass spectrometry, which causes molecules to break down into their constituent amino acids.
The drawback to ETD alone is that it often doesn’t fragment all of the peptide sequence. So the team combined ETD with a technique to increase the charge of cysteine-containing peptide toxins. A higher charge state caused the peptide toxins to fragment more than they would have using ETD alone.
“This method removes the necessity for collecting large numbers of animals and pooling their venoms which was required previously for more classical approaches to sequencing conotoxins,” Professor Alewood said.
The team also developed a computer program that helps fill in any gaps by checking partial sequences against a database containing the DNA code for known venom peptides.
The team consisted of Dr Beatrix Ueberheide, Dr David Fenyo and Professor Brian Chait from Rockefeller University and Professor Alewood from The University of Queensland. The research was published in Proceedings of the National Academy of Sciences U.S.A.(Proc. Natl. Acad. Sci. U.S.A., 2009, 106, 6910–15).
Contact: Professor Paul Alewood - 07 3346 2982
Bronwyn Adams - 07 3346 2134 or 0418 575 247