Venom Yields Treasure Trove

Novel sulfated nucleosides that are likely to have potent biological activity have been identified in spider venom through the use of a new analytical approach based on nuclear magnetic resonance spectroscopy.

The approach, developed at Cornell University, relies on the acquisition of a set of NMR spectra from the entire crude venom without prior purification. Postdoc Andrew E. Taggi, chemistry professor Jerrold Meinwald, and senior research associate Frank C. Schroeder used the approach to identify at least seven ribonucleoside mono- and disulfates derived from guanosine and xanthosine in venom secreted by the hobo spider, Tegenaria agrestis [J. Am. Chem. Soc., published online July 28,

http://dx.doi.org/10.1021/ja047416n]. Some of the compounds are glycosylated derivatives.

"Spider venoms are comprised of complicated mixtures of proteins, polypeptides, free amino acids, polyamines, nucleosides, and other compounds," Schroeder says. "With more than 40,000 known--and probably many more unknown--species of spiders, of which only a small percentage have been investigated chemically, the potential for new and interesting discoveries seems vast."

The Cornell methodology employs a set of standard two-dimensional NMR experiments that, according to Schroeder, are part of the toolbox of any contemporary natural products chemist.

"The presence of so many different compounds in spider venom dramatically increases the difficulty of interpreting the spectra," Schroeder notes. "In this situation, one specific 2-D NMR experiment, DQF-COSY [double-quantum filtered-correlated spectroscopy], is especially helpful. It allows us to distinguish clearly between groups of NMR signals derived from different compounds."

The presence of sulfated nucleosides in spider venom, Taggi points out, suggests that they act in some fashion as neurotoxins, possibly in conjunction with other compounds present in the secretion.

Schroeder explains that the use of NMR spectroscopy to characterize unpurified venom allows for an impartial view of its composition. By contrast, standard analytical approaches that employ extraction and purification schemes are likely to favor some classes of compounds while overlooking others.

The Cornell researchers are currently using their NMR-based analytical approach to screen a large number of spider venoms from a diverse set of species for the presence of sulfated nucleosides and other previously overlooked compounds.