A team of scientists headed by Prof Paul Alewood of the University of Queensland in Brisbane, Australia, has discovered more than 3,000 new peptide toxins hidden deep within the venom of a predatory sea snail, Conus episcopatus.
Conus episcopatus, 6.4 cm, Thailand. Image credit: Alexander Medvedev / CC BY-SA 3.0.
Cone snails are marine gastropod mollusks, just as conch, octopi and squid, with more than 700 valid species currently recognized in the World Register of Marine Species.
Over the last 30 million years, these species have evolved sophisticated predatory and defense strategies.
Their venom apparatus is responsible for the biosynthesis and maturation of neurotoxins that, once injected in the prey or predator (fish, mollusks, or worms), act as fast-acting paralytics.
“Cone snail venoms are a complex cocktail of many chemicals and most of these toxins have been overlooked in the past,” Prof Alewood said.
He and his colleagues from the University of Queensland have focused their research on the venom of the marine snail Conus episcopatus and have published a study in the Proceedings of the National Academy of Sciences.
They used biochemical and bioinformatics tools to develop a new method to analyze the structure of the venom toxins, allowing them to delve deeper than ever before.
“Cone snail venom is known to contain toxins proven to be valuable drug leads. This study gives the first-ever snapshot of the toxins that exist in the venom of a single cone snail,” Prof Alewood said.
Using their new method that involved accurately measuring and analyzing the structure, activity and composition of the diverse range of proteins within venom, the scientists discovered the highest number of peptides produced in a single cone snail.
The researchers hope the new molecules will be promising leads for new drugs to treat pain and cancer.
“We also discovered six original ‘frameworks’ – 3D-shaped molecules suitable as drug leads – which we expect will support drug development in the near future,” Prof Alewood said.
There are 25 known frameworks discovered over the past 25 years, many of which have already led to a drug or drug lead for several diseases.
“We expect these newly-discovered frameworks will also lead to new medications, which can be used to treat pain, cancer and a range of other diseases,” Prof Alewood added.
_____
Vincent Lavergne et al. Optimized deep-targeted proteotranscriptomic profiling reveals unexplored Conus toxin diversity and novel cysteine frameworks. PNAS, published online July 06, 2015; doi: 10.1073/pnas.1501334112
