Pharmacokinetic (PK) extension is no longer just a means to create improved second generation biologics (so-called biobetters), but constitutes an accepted strategy in biopharmaceutical drug development today. Although PEGylation has become a widely applied methodology to furnish therapeutic proteins and peptides with prolonged plasma half-life, the immunogenicity and missing biodegradability of this synthetic polymer has prompted an evident need for alternatives. PASylation is based on biological polypeptides made of the small l-amino acids Pro, Ala and/or Ser (PAS), which adopt a random coil structure in aqueous buffers with surprisingly similar biophysical properties as PEG. In contrast, PAS sequences can be conjugated to pharmaceutically active proteins and peptides both via chemical coupling and at the genetic level, as so-called fusion proteins. PASylation has been successfully applied to numerous biologics, including cytokines, growth factors, antibody fragments, enzymes as well as various peptides, and validated in diverse animal models, from mice to monkeys. Here we compare PASylation with other current strategies for half-life extension and we discuss the utility of these approaches for the design of innovative peptide-based therapeutics.

药代动力学（PK）扩展不再仅仅是创造改进的第二代生物制剂（所谓的生物制剂）的手段，而是当今生物制药开发中公认的策略。尽管聚乙二醇化已成为提供具有延长的血浆半衰期的治疗性蛋白质和肽的一种广泛应用的方法，但是这种合成聚合物的免疫原性和缺少的生物降解性促使人们明显需要替代品。PAS化的基础上进行小的生物多肽升-氨基酸Pro，Ala和/或Ser（PAS），它们在水性缓冲液中采用无规卷曲结构，具有与PEG惊人的相似的生物物理特性。相反，PAS序列可以通过化学偶联和在遗传水平上与药物活性蛋白和肽缀合，即所谓的融合蛋白。PASylation已成功应用于多种生物制剂，包括细胞因子，生长因子，抗体片段，酶以及各种肽，并已在从小鼠到猴子的多种动物模型中得到验证。在这里，我们将PASylation与其他目前的半衰期延长策略进行了比较，并讨论了这些方法在设计创新的基于肽的疗法中的实用性。