CHAPTER 2: The Structural Universe of Disulfide-Rich Venom Peptides

Animal venoms are typically complex mixtures of inorganic salts, small organic molecules (<1 kDa), polypeptides (2–9 kDa), and high molecular weight proteins including enzymes (>10 kDa). However, the dominant components of most venoms are peptides and proteins. Since most venoms are delivered parenterally to their prey (e.g., via barbs, fangs, or harpoons), these venom peptides and proteins must be stable enough to reach their sites of action before being degraded or excreted. This has resulted in a preference for recruitment into the venom of highly stable molecular scaffolds that are resistant to degradation by proteases. Consequently, the vast majority of venom peptides and proteins are cross-braced by one or more disulfide bridges and have well-defined tertiary structures. The aim of this chapter is to introduce readers to the disulfide-rich architectures that have been recruited multiple times into different animal venoms or that are common in certain venomous taxa. Issues relevant to the therapeutic use of venom peptides will be briefly discussed.