PDF(Pubmed)
Abstract：
Relaxin-2 is a peptide hormone with important roles in human cardiovascular and reproductive biology. Its ability to activate cellular responses such as vasodilation, angiogenesis, and anti-inflammatory and antifibrotic effects has led to significant interest in using relaxin-2 as a therapeutic for heart failure and several fibrotic conditions. However, recombinant relaxin-2 has a very short serum half-life, limiting its clinical applications. Here, we present protein engineering efforts targeting the relaxin-2 hormone in order to increase its serum half-life while maintaining its ability to activate the G protein-coupled receptor RXFP1. To achieve this, we optimized a fusion between relaxin-2 and an antibody Fc fragment, generating a version of the hormone with a circulating half-life of around 3 to 5 days in mice while retaining potent agonist activity at the RXFP1 receptor both in vitro and in vivo.
摘要：
松弛素-2是一种肽类激素，在人类心血管和生殖生物学中具有重要作用。它激活细胞反应如血管舒张的能力，血管生成,抗炎和抗纤维化作用引起了人们对使用松弛素-2作为心力衰竭和几种纤维化病症的治疗剂的极大兴趣。然而,重组松弛素-2具有非常短的血清半衰期,限制其临床应用。这里,我们提出了针对松弛素-2激素的蛋白质工程努力，以增加其血清半衰期，同时保持其激活G蛋白偶联受体RXFP1的能力。为了实现这一点，我们优化了松弛素-2和抗体Fc片段之间的融合，在小鼠体内产生一种循环半衰期约为3至5天的激素，同时在体内和体外均保留对RXFP1受体的有效激动剂活性。
