Synthetic APELIN Fatty Acid Conjugates with an Improved Half-Life

Abstract

The invention relates to a conjugate, or one of its pharmaceutically acceptable salts, comprising a synthetic polypeptide of formula i: qrprlc*-hkgp-(nle)-c*-f(i) or one of its amides or esters; and a fatty acid selected from: wherein said fatty acid is covalently linked to the n-terminal end of the peptide via one of its carboxylic acid functionalities, optionally via a polyethylene glycol linker; and wherein the two cysteine ​​amino acids marked with "*" form a disulfide bond between the thiol functionalities of their side chain. The conjugates are agonists of the apj receptor.The invention also relates to a method of manufacturing the conjugates of the invention and its therapeutic uses such as the treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic heart disease, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, strokes, transient ischemic attacks, traumatic brain injury, amyotrophic lateral sclerosis, burns (including sunburn) and preeclampsia.