The rapid renal clearance of peptides in vivo limits this attractive platform for the treatment of a broad range of diseases that require prolonged drug half-lives. An intriguing approach for extending peptide circulation times works through a 'piggy-back' strategy in which peptides bind via a ligand to the long-lived serum protein albumin. In accordance with this strategy, we developed an easily synthesized albumin-binding ligand based on a peptide-fatty acid chimera that has a high affinity for human albumin (K_d=39 nM). This ligand prolongs the elimination half-life of cyclic peptides in rats 25-fold to over seven hours. Conjugation to a peptide factor XII inhibitor developed for anti-thrombotic therapy extends the half-life from 13 minutes to over five hours, inhibiting coagulation for eight hours in rabbits. This high-affinity albumin ligand could potentially extend the half-life of peptides in human to several days, substantially broadening the application range of peptides as therapeutics.

中文翻译：

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酰化的七肽以高亲和力结合白蛋白，并作为标签提供长效肽的应用。

体内肽的快速肾脏清除限制了该吸引人的平台，该平台可用于治疗需要延长药物半衰期的多种疾病。延长肽循环时间的一种有趣方法是通过“背负式”（piggy-back）策略工作，在这种策略中，肽通过配体与长寿的血清蛋白白蛋白结合。按照这种策略，我们开发了一种基于易于合成的，与人白蛋白（K _d亲和力高的肽-脂肪酸嵌合体）的白蛋白结合配体。= 39 nM）。该配体将环肽在大鼠中的消除半衰期延长了25倍至7个小时以上。与开发用于抗血栓治疗的肽因子XII抑制剂的缀合将半衰期从13分钟延长至超过5小时，从而在兔体内抑制了8小时的凝血。这种高亲和力的白蛋白配体可以将多肽在人体内的半衰期延长至几天，从而大大拓宽了多肽作为治疗剂的应用范围。