Synthetic relaxins

• Relaxin-2 and relaxin-3 are regulatory peptides that are structurally related to insulin.
• Relaxin-2 has pleiotropic actions including as a cardiovascular stimulant.
• Relaxin-3 is a neuropeptide involved in stress and metabolic control.
• Their complex 2-chain, 3-disulfide bond structures are a unique synthesis challenge.
• Efficient chemical and DNA-directed synthesis methods have been devised.

The relaxin subfamily of peptides within the human insulin superfamily consists of seven members including relaxin-2 and relaxin-3. The former is a pleiotropic hormone that is a vasodilator and cardiac stimulant in the cardiovascular system and an antifibrotic agent whereas the latter is primarily a neuropeptide involved in stress and metabolic control. Both possess the unique three-disulfide heterodimeric peptide structure of insulin. Consequently, the synthesis, both chemical and biological, of relaxin-2 and relaxin-3 has long represented a special challenge to further understanding their structural and functional relationships. This review highlights past and recent developments in the use of chemical and recombinant DNA methods of synthesis of these peptides and current resulting knowledge of their biology.