The relaxin peptide family--structure, function and clinical applications.
The relaxin peptide family in humans consists of seven members, relaxin-1, -2 and -3 and insulin-like (INSL) peptides 3, 4, 5 and 6. It is an offshoot of the large insulin superfamily. Each member consists of two chains, commonly referred to as A and B, which are held together by two inter-chain disulfide bonds and another intra-chain disulfide bond present within the A chain. The cysteine residues present in each chain, together with the distinctive disulfide bonding pattern, are conserved across all members of the superfamily. The chemical synthesis of these complex peptides poses a significant challenge. In the past, random combination of the two synthetic S-reduced chains under oxidizing conditions was utilized to form the three disulfide bonds. Nowadays, with the aid of highly efficient solid phase peptide synthesis methodologies, in conjunction with selective S-thiol-protecting groups, combination of individual A- and B- chains by sequential chemical formation of each of the three disulfide bonds is now possible resulting in good yields of these peptides. The relaxin peptide family members bind to G-protein coupled receptors (GPCRs) which have been classified as relaxin family peptide (RXFP) receptors. The various unique receptor-ligand interactions are outlined in this review, together with the physiological roles of the relaxin peptide family members and lastly their past and present clinical applications.
Chan
Linda Jiaying
LJ
Florey Neuroscience Institutes, The University of Melbourne, Victoria, Australia.
Hossain
Mohammed Akhter
MA
Samuel
Chrishan S
CS
Separovic
Frances
F
Wade
John D
JD
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D012065:Relaxin / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use*
D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C033395:relaxin receptors; D012065:Relaxin