Apelin is an important mammalian peptide hormone with a range of physiological roles, especially in the cardiovascular system. The apelinergic system is a promising target for treatment of disease, but this remains to be realized due to rapid proteolysis of apelin-derived peptides by proteases, including neprilysin (NEP). The synthetic analogues modified within the NEP degradation site (“RPRL” motif) showed improved in vitro proteolytic stability while maintaining receptor-binding affinities, with three candidate peptides retaining full cardiovascular activities for potential therapeutic application. Many such analogues proved physiologically inactive even with relatively conservative modifications, highlighting the importance of this region for full agonist activity of this peptide hormone.

中文翻译：

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Apelin肽的“ RPRL”区域内的合成修饰：对心血管活性以及对中性溶酶和血浆降解的稳定性的影响

Apelin是一种重要的哺乳动物肽激素，具有多种生理作用，尤其是在心血管系统中。Apelinergic系统是治疗疾病的有希望的靶标，但是由于蛋白酶（包括neprilysin（NEP））对apelin衍生的肽进行了快速蛋白水解，因此仍有待实现。在NEP降解位点（“ RPRL”基序）内修饰的合成类似物显示出改善的体外蛋白水解稳定性，同时保持受体结合亲和力，其中三种候选肽保留了完整的心血管活性，可用于潜在的治疗应用。即使具有相对保守的修饰，许多此类类似物也被证明在生理上是无活性的，从而突显了该区域对于该肽激素的完全激动剂活性的重要性。