By Roger Highfield
A trove of potential drugs for conditions as diverse as impotence and arthritis could emerge from a study of venom from a potentially deadly spider.
Venom already has provided leads for therapeutics to treat arthritis and erectile dysfunction, and compounds found in venom are being studied to create organic, earth-friendly pesticides.
Now scientists have analysed the components of the venom of more than 70 species of spiders, including the brown recluse, whose bites are known to cause painful, gangrenous lesions. Sometimes a limb is lost, even a life.
Prof Frank Schroeder and Prof Jerrold Meinwald of Cornell University, Ithaca, as reported in the Proceedings of the National Academy of Sciences, used a clever way to take a molecular snapshot of venom, without having to process it in any way.
They used a method called nuclear magnetic resonance spectroscopy, which studies the structure of molecules in the venom, and combined it with a method called mass spectrometry, which in effect weighs molecules.
"We show how using NMR spectroscopy for the analysis of a complex mixtures such as spider venom one can find new and entirely unexpected chemistry," said Prof Schroeder.
"Our research shows that brown recluse venom contains important, previously undetected components that have been overlooked."
The venom contains a blend of very big and small molecules. One of the latter was an entirely new structural class that had been missed by earlier studies.
These compounds, called sulphated nucleosides, are based on one of the building blocks of RNA, the genetic material, with one small but important structural modification: a phosphate group is replaced by a sulphate.
"Because we just recently identified these new nucleoside derivatives, we don't know much about their biological activity yet. It seems likely that they contribute to the toxic properties of the venom, but we can't yet say anything about their mode of action."
The venom also contained messenger chemicals that work in the brain and on nerves.
In addition, the venom has been shown to contain several different proteins, including enzymes such as hyaluronidase, deoxyribonuclease, ribonuclease, alkaline phosphatase, and lipase, which help to break down tissue, among other things.
Among these enzymes, sphingomyelinase D is thought to be the protein component responsible for most of the tissue destruction caused by brown recluse spider bites.
"One important aspect of our work is that it highlights that we still know very little about the chemistry of life," said Prof Schroeder.
"Even in case of a spider species such as the brown recluse, which has undergone extensive study by both chemists and biologists, our knowledge of the basic composition of its venom turned out to be very incomplete.
It seems likely that using new technology for chemical analysis will reveal many more such surprises, not only in spiders, but also in many other life forms, including vertebrates and mammals."