PASylation® technology comprises the conjugation – via genetic fusion or chemical coupling – of pharmacologically active compounds, such as proteins, peptides and low molecular weight drugs, with natively disordered biosynthetic polymers made of the small L-amino acids Pro, Ala and/or Ser. Such proline/alanine-rich sequences (PAS) are highly soluble in physiological solution and stably adopt random coil conformation, which results in an expanded hydrodynamic volume. Consequently, PAS-drug conjugates show retarded kidney filtration and drastically prolonged pharmacokinetics (PK) in vivo. The intrinsically uncharged PAS polypeptides do not interfere with the pharmacological activity of the drug component and show high stability in plasma as well as no immunogenicity, while undergoing quick degradation and metabolization after cellular uptake. PASylation has been successfully applied to a wide range of pharmacologically active proteins and peptides, including hormones, cytokines, antibody fragments and enzymes, as well as nanocarriers. This review discusses the fundamental concepts of PASylation technology and recent advances in preclinical applications.

PASylation®技术包括通过遗传融合或化学偶联将诸如蛋白质，肽和低分子量药物之类的药理活性化合物与由小分子L-氨基酸Pro，Ala和/或Ser制成的天然无序生物合成聚合物相结合。 。这样的富含脯氨酸/丙氨酸的序列（PAS）在生理溶液中高度可溶，并且稳定地采用无规卷曲构象，这导致了更大的流体动力学体积。因此，PAS-药物偶联物在体内显示出延迟的肾脏滤过和显着延长的药代动力学（PK）。内在不带电的PAS多肽不会干扰药物成分的药理活性，并且在血浆中显示出高稳定性，并且没有免疫原性，同时在细胞摄取后会迅速降解和代谢。PASylation已成功应用于各种药理活性蛋白和多肽，包括激素，细胞因子，抗体片段和酶以及纳米载体。这篇综述讨论了PASylation技术的基本概念以及临床前应用的最新进展。