%0 Journal Article
%T Engineering and Characterization of a Long-Half-Life Relaxin Receptor RXFP1 Agonist.
%A Erlandson SC
%A Wang J
%A Jiang H
%A Osei-Owusu J
%A Rockman HA
%A Kruse AC
%J Mol Pharm
%V 21
%N 9
%D 2024 Sep 2
%M 39134056
%F 5.364
%R 10.1021/acs.molpharmaceut.4c00368
%X 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.