Conus peptides

One major recent development in the area of natural products is the discovery and subsequent medicinal application of the toxic peptides from cone snails. These Conus peptides, several of which contain a 6-bromotryptophan amino acid, are finding utility for the treatment of neuropathic pain and other neurological conditions (1074-1078). For example, oo-conopeptide MVIIA (Ziconotide, trade name Prialt) has been approved by the US FDA since 2004 for the treatment of severe pain. It is estimated that the 500-700 species of cone snails (Conus genus) contain... 

Myers RA, Cruz LJ, Rivier JE, Olivera BM (1993) Conus Peptides as Chemical Probes for Receptors and Ion Channels. Chem Rev 93 1923... 

Lirazan MB, Craig AG, Shetty R, Walker CS, Olivera BM, Cruz LJ (1999) Multiple Bromotryptophan and y-Carboxyglutamate Residues in a Conus Peptide. Philippine J Sci 128 239... 

Monje VD, Haack JA, Naisbitt SR, Miljanich G, Ramachandran J, Nasdasdi L, Olivera BM, Hillyard DR, Gray WR (1993) A new Conus peptide ligand for Ca channel subtypes. Neuropharmacology 32 1141-9... 

Given the enormous library of peptidic natural products found in the venom of cone snails, the discovery of conopeptides is a task that will occupy researchers for decades to come. Only a small fraction of the existing Conus peptides library has been characterized nevertheless, new peptidic arrangements with novel bioactivities are constantly described in the literature. 

McIntosh, ).M., Santos, A.D., Olivera, B.M. Conus peptides targeted to specific nicotinic... 

Hillyard DR, Monje VD, Mintz IM, Bean BP, Nadasdi L, Ramachandran J, Miljanich G, Azimi-Zoonooz A, McIntosh JM, Cruz LJ. A new Conus peptide ligand for mammalian presynaptic Ca channels. Neuron 1992 9(l) 69-77. 

Biggs, J.S., Rosenfeld, Y., Shai, Y, and Olivera, B.M. (2007) Conolysin-Mt A Conus peptide that disrupt cellular membranes. Biochemistry, 46,12586-12593. 

Jacobsen, R., Jimenez, E.C., Grilley, M Watldns, M., Hillyard, D., Cruz, L.J., and Olivera, B.M. (1998) The contryphans a o-tryptophane[Pg.1432]

Krishnamurthy, T, Prabhakaran, M., and Long, S,R, (1996) Mass spectrometric investigations on Conus peptides, Toxicon, 34, 1345-1359. 

Close to 90% of the naturally-occurring Conus peptides have four to six cysteine residues involved in disulfide bonds. Most of the peptides found so far belong to the three structural classes (see Table 1) corresponding to different arrangements of cysteine residues. The most abundant structural class appears to be the 6-Cys/4-loop cysteine framework typified by the co-conotoxins (C—C—CC—C—C), followed by the 6-Cys/3-loop framework represented by p-conotoxins (CC—C—C—CC), and the 4-Cys/2-loop framework of the a-conotoxins (CC—C—C). This structural motif, i.e., the presence of multiple disulfide bonds, is responsible for maintaining many Conus peptides in a fairly rigid and compact conformation needed for the rapid transport of the peptides to their macromolecular targets. 

Among Conus peptides, co-conotoxins have received the most attention because they are widely used as pharmacological tools for differentiating subtypes of calcium channels. Since two reviews discussing co-conotoxins have been published recently (Olivera et al.. 

Cruz, L. J., Ramilo, C. A., Corpuz, G. P. and Olivera, B. M. 1992. Conus peptides phylogenetic range of biological activity. Biol Bull. 183 159-164. 

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