| abstract |
Refers to a modified relaxin polypeptide comprising an unnaturally encoded amino acid, wherein: a) the modified relaxin polypeptide comprises the relaxin A chain polypeptide of SEQ ID NO: 4 and the B chain polypeptide of relaxin of SEQ ID NO: 5 or SEQ ID NO: 6, which is substituted with an unnaturally encoded amino acid in a selected position consisting of residues 1, 2, 5, 13 and 18 of chain A and residues 5, 7 and 25 of chain B; b) the unnaturally encoded amino acid has the structure (Z) where R is any substituent other than the side chain found in alanine, arginine, among others; c) said unnaturally encoded amino acid is linked to a pharmacokinetic enhancer of formula (II) comprising a peptide component of 2 to 30 amino acids and a half-life extension portion of Formula (I); and d) said peptide component comprises Glu, Glu (gamma), GGGGS-Glu (gamma) (SEQ ID NO: 139); among others. Said polypeptide is biologically active, capable of increasing renal blood flow after administration, and has a longer half-life in vivo, being useful for the treatment of cardiovascular conditions and / or fibrosis-related conditions. It also refers to a pharmaceutical composition containing said polypeptide |