Conotoxins as research tools and drug leads

The complex mixture of biologically active peptides that constitute the venom of Conus species provides a rich source of ion channel neurotoxins. These peptides, commonly known as conotoxins, exhibit a high degree of selectivity and potency for different ion channels and their subtypes making them invaluable tools for unravelling the secrets of the nervous system. Furthermore, several conotoxin molecules have profound applications in drug discovery, with some examples currently undergoing clinical trials. Despite their relatively easy access by chemical synthesis, rapid access to libraries of conotoxin analogues for use in structure-activity relationship studies still poses a significant limitation. This is exacerbated in conotoxins containing multiple disulfide bonds, which often require synthetic strategies utilising several steps. This review will examine the structure and activity of some of the known classes of conotoxins and will highlight their potential as neuropharmacological tools and as drug leads. Some of the classical and more recent approaches to the chemical synthesis of conotoxins, particularly with respect to the controlled formation of disulfide bonds will be discussed in detail. Finally, some examples of structure-activity relationship studies will be discussed, as well as some novel approaches for designing conotoxin analogues.

The open secret: Hiding and revealing sexuality in the roman de moeurs (1880-1905)

Beginning with the sole literary text that does figure at any length in the first volume of Foucault's history--Diderot's Les Bijoux indiscrets, which dates from 1748--Cryle examines some semiotic routines involved in that telling of secrets, and to understand more about scientia sexualis through its literary development. He tries to show that narratives of the time tended to gather the mysterious, the unknown, and the generally inscrutable in the same functional place, holding them close to a thematics of the sexual. And returns to eighteenth-century texts from time to time in order to mark this as a fundamental shift in the literary constitution of sexual knowledge.