{Reference Type}: Journal Article
{Title}: Engineering and Characterization of a Long-Half-Life Relaxin Receptor RXFP1 Agonist.
{Author}: Erlandson SC;Wang J;Jiang H;Osei-Owusu J;Rockman HA;Kruse AC;
{Journal}: Mol Pharm
{Volume}: 21
{Issue}: 9
{Year}: 2024 Sep 2
{Factor}: 5.364
{DOI}: 10.1021/acs.molpharmaceut.4c00368
{Abstract}: Relaxin-2 is a peptide hormone with important roles in human cardiovascular and reproductive biology. Its ability to activate cellular responses such as vasodilation, angiogenesis, and anti-inflammatory and antifibrotic effects has led to significant interest in using relaxin-2 as a therapeutic for heart failure and several fibrotic conditions. However, recombinant relaxin-2 has a very short serum half-life, limiting its clinical applications. Here, we present protein engineering efforts targeting the relaxin-2 hormone in order to increase its serum half-life while maintaining its ability to activate the G protein-coupled receptor RXFP1. To achieve this, we optimized a fusion between relaxin-2 and an antibody Fc fragment, generating a version of the hormone with a circulating half-life of around 3 to 5 days in mice while retaining potent agonist activity at the RXFP1 receptor both in vitro and in vivo.