Drugs from slugs. Part II--conopeptide bioengineering

The biological transformation of toxins as research probes, or as pharmaceutical drug leads, is an onerous and drawn out process. Issues regarding changes to pharmacological specificity, desired potency, and bioavailability are compounded naturally by their inherent toxicity. These often scuttle their progress as they move up the narrowing drug development pipeline. Yet one class of peptide toxins, from the genus Conus, has in many ways spearheaded the expansion of new peptide bioengineering techniques to aid peptide toxin pharmaceutical development. What has now emerged is the sequential bioengineering of new research probes and drug leads that owe their lineage to these highly potent and isoform specific peptides. Here we discuss the progressive bioengineering steps that many conopeptides have transitioned through, and specifically illustrate some of the biochemical approaches that have been established to maximize their biological research potential and pharmaceutical worth.