The invention provides a bioconjugates comprising a synthetic polypeptide of Formula 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 half-life extending moiety wherein the peptide and the half-life extending moiety are covalently linked or fuse, optionally via a linker. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the bioconjugates of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, 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.本發明提供一種包含式I'之合成多肽的生物結合物：或其醯胺、酯或鹽，其中X1、X2、X3、X4、X5、X6、X7、X8、X9、X10、X11、X12及X13係如本文所定義及半衰期延長部分，其中該肽及該半衰期延長部分視情況經由連接子共價連接或融合。該多肽為APJ受體之促效劑。本發明亦關於一種用於製造本發明之生物結合物之方法，及其治療性用途，諸如治療或預防急性失代償心臟衰竭(ADHF)、慢性心臟衰竭、肺高血壓、心房纖維性顫動、布魯加達症候群(Brugada syndrome)、心室性心搏過速、動脈粥樣硬化、高血壓、再狹窄、缺血性心血管疾病、心肌病、心臟纖維化、心律不整、水滯留、糖尿病(包括妊娠期糖尿病)、肥胖症、周邊動脈疾病、腦血管意外、短暫性缺血性發作、外傷性腦損傷、肌萎縮性側索硬化、燒傷(包括曬傷)及子癇前症。本發明另外提供藥理學活性劑之組合與醫藥組合物。
