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Engineering and Characterization of a Long-Half-Life Relaxin Receptor RXFP1 Agonist.

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.

SUBMITTER: Erlandson SC

PROVIDER: S-EPMC11372834 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature

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Engineering and Characterization of a Long-Half-Life Relaxin Receptor RXFP1 Agonist.

Erlandson Sarah C SC Wang Jialu J Jiang Haoran H Osei-Owusu James J Rockman Howard A HA Kruse Andrew C AC

Molecular pharmaceutics 20240812 9

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 targeti ...[more]

PMID: 39134056

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