The Terebridae are a promising family within the Conoidea. Similar to cone snails terebrids possess venom peptide toxins that appear rich in variety and functional applications (Table ). Preliminary results conducting biochemical [26
] and molecular [27
] characterization of teretoxins indicate they are very similar in structure to cone snail toxins. Teretoxins thus far identified appear to be larger than conotoxins (≥ 40 amino acids) and do not have posttranslation modifications, a feature commonly found in conotoxins. The lack of posttranslation modifications makes teretoxins an attractive target for analysis using mass spectrometry. Recently Ueberheide and colleagues [47
] developed a mass spectrometry approach for elucidating toxin sequences from cone snails that utilizes the electron-transfer dissociation (ETD) method for tandem mass spectrometry. ETD is used to increase sequence coverage and improve mass detection to limits well beyond those of Edman sequencing and previous mass spectrometry methods. While limited by the current high cost of advanced mass spectrometry hardware, this technique appears to be a viable complement to the Concerted Discovery Strategy (CDS), and can be used both to confirm the expression and characterization of newly discovered teretoxins. While thus far applied only to cone snail toxins, the ETD inspired method also holds promise for identifying the primary amino-acid sequences of peptide toxins from terebrids and other venomous organisms. In addition, recombinant techniques such as the recently described tethered-toxin approach [48
] facilitate the synthesis and folding of larger peptidic toxins.
Although not traditionally the molecular compound of choice for drug discovery, peptides, and especially peptidic toxins, are becoming increasingly important in the development of novel drug discovery pipelines. The N-type calcium (Ca2+
) channel analgesic ziconotide, the first conotoxin drug, is striking for the molecular target and function combination it identified [19
]. Prior to ziconotide's discovery Ca2+
channels were not readily recognized as targets for pain alleviation. Similar to Ziconotide, an ω conotoxin, several other conotoxin families including, μ-conotoxins, which target voltage-gated Na+
channels, k- and kM-conotoxins, which target K+
channels, and conantokins, which target NMDA receptors, are under various stages of pharmaceutical development [5
]. The potential applications of these conotoxins vary from pain, to epilepsy, and cardioprotective agents. In addition to conotoxins, peptidic toxins from scorpions, snakes and spiders, such as candoxin (Alzheimer's disease) [53
], and α-Bgtx (myasthenic autoimmune response) [54
] are making an impact in pharmacological developments. These peptides and the organisms that produce them are instrumental in identifying the next generation of therapeutics.
A discovery strategy such as CDS, which takes into account the divergent characteristic of peptide toxins from biodiverse organisms, paired together with current advances in peptide/proteomics, genomic and bioinformatic technologies provides a paradigm for investigating peptidic natural products that significantly enhances the identification of pharmacologically useful bioactive compounds. Current integrative initiatives that utilize ecological, genomic, proteomic, and functional activity based data of toxins, such as the cone snail genome project for health, CONCO http://www.conco.eu
, and Venomics [56
], will be useful in deciphering the potential and challenges ahead for terebrid toxin characterization.