Multiple Disulfide Bridges

Disulfide linkages, also known as disulfide bridges, are reversible covalent connections that can form between two side chain thiol groups and can occur between cysteine (Cys) residues in proteins and peptides. Disulfide bonds give linear peptide sequences structural limitations that increase molecular stiffness and more stable secondary structures. Peptides with a high disulfide content are less likely to be broken down by enzymes and can occasionally boost binding affinity to the relevant receptor.

Disulfide-rich peptides that are conformationally stable have given rise to numerous powerful and selective peptide classes. The host-defense peptides (such as -defensins and -defensins) and poison peptides from scorpions, cone snails, snakes, and spiders are significant classes with a variety of therapeutic applications. Conotoxin and chlorotoxin are strong ion channel blockers that have been proposed as cancer and chronic pain therapies.