It is well known that the short half-life limits the therapeutic potential of relaxin-2, a peptide hormone with positive cardiovascular effects. However, a similar problem was solved with the hormone GLP-1 by incorporating an unnatural amino acid into the sequence and modifying the lysine side chain with a fatty acid. Perhaps such approaches are also applicable in the case of relaxin-2. Direct chemical synthesis of relaxin-2 analogues appears to be a good tool for optimising molecules for primary screening of biological activity. As an example, we have synthesised a palmitoyl derivative of relaxin-2. Technical details can be found in the attached file.
