AI Article Synopsis
- Human relaxin-2 is a hormone important for mediating blood flow changes during pregnancy and has potential benefits in treating acute heart failure, but its clinical use is limited due to a short half-life and requirement for intravenous administration.
- Researchers developed long-acting relaxin peptide mimetics by modifying the B-chain of relaxin, leading to simpler and more potent peptide agonists for the relaxin receptor RXFP1.
- These new lipidated peptide agonists demonstrated high activity, better bioavailability when taken subcutaneously, and longer half-lives, making them promising candidates for wider therapeutic use.
Article Abstract
The insulin-like peptide human relaxin-2 was identified as a hormone that, among other biological functions, mediates the hemodynamic changes occurring during pregnancy. Recombinant relaxin-2 (serelaxin) has shown beneficial effects in acute heart failure, but its full therapeutic potential has been hampered by its short half-life and the need for intravenous administration limiting its use to intensive care units. In this study, we report the development of long-acting potent single-chain relaxin peptide mimetics. Modifications in the B-chain of relaxin, such as the introduction of specific mutations and the trimming of the sequence to an optimal size, resulted in potent, structurally simplified peptide agonists of the relaxin receptor Relaxin Family Peptide Receptor 1 (RXFP1) (, ). Introduction of suitable spacers and fatty acids led to the identification of single-chain lipidated peptide agonists of RXFP1, with sub-nanomolar activity, high subcutaneous bioavailability, extended half-lives, and efficacy (, ).
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| http://dx.doi.org/10.1021/acs.jmedchem.0c01533 | DOI Listing |
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