The minimal active structure of human relaxin-2.

摘要: H2 relaxin is a peptide hormone associated with number of therapeutically relevant physiological effects, including regulation collagen metabolism and multiple vascular control pathways. It currently in phase III clinical trials for the treatment acute heart failure due to its ability induce vasodilation influence renal function. comprises 53 amino acids characterized by two separate polypeptide chains (A-B) that are cross-linked three disulfide bonds. This size complex structure represents considerable challenge chemical synthesis relaxin, major limiting factor exploration modifications derivatizations this peptide, optimize effect drug-like characteristics. To address issue, we describe solid structural functional evaluation 24 analogues truncations at termini chains. We show it possible significantly truncate both N C B-chain while still retaining potent biological activity. suggests these regions not critical interactions receptor, RXFP1. In contrast, do reduce activity related receptor RXFP2 improving RXFP1 selectivity. addition new mechanistic insights into function study identifies active core 38 acids. minimized shows similar antifibrotic as native when tested human BJ3 cells thus an attractive receptor-selective lead development novel therapeutics.