| abstract |
The invention provides bioconjugates comprising a synthetic polypeptide of the formula I ': X1-X2-X3-X4-X5-X6-X7-X8-X9 -X10-X11-X12-X13 (I') or an amide, an ester , or a salt thereof, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein, and a prolonging fraction of the half-life, in where the peptide and the prolonging fraction of the half-life are linked or fused in a covalent manner, optionally by means of a linker. Polypeptides are agonists of the APJ receptor. The invention also relates to a method for the preparation of the bioconjugates of the invention, and to their therapeutic uses, such as the treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, syndrome Brugada, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arteriopathy, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, Amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition. |