模拟PEG的聚多肽融合技术研究进展

Advances in recombinant polypeptide mimetics of PEG

多肽和蛋白质药物特异性高、生物活性高,但是稳定性差、血浆半衰期短,限制了其在临床上的应用。PEG修饰技术是蛋白质长效化的常用手段,但仍存在一定的缺点,因此近年来研究者开发了模拟PEG的聚多肽融合技术。聚多肽融合技术是通过DNA重组技术将蛋白质药物与特殊的氨基酸序列融合,增加药物的流体动力学体积或产生电荷效应,从而延缓肾小球滤过,增加融合蛋白的血浆半衰期。本文对已有的多种聚多肽及其在蛋白质长效化方面的研究进行综述。

Peptide and protein biologics possess high specificity and high biological activity, but their poor stabil- ity and short plasma half-life have limited clinical application. One established strategy to increase half-life of therapeutic proteins is chemical conjugation of the biologic with PEG. Nevertheless, PEGylation technology has some drawbacks, so recombinant polypeptide mimetics of PEG have gradually developed in recent years. Pharma- ceutically active protein can be fused with specific amino acid sequences using recombinant DNA technology, and then increase hydrodynamic volume or produce charge effect, which retards kidney filtration and eventually prolongs the half-life. This article mainly reviews kinds of polypeptides and the research progress in half-life extension of therapeutic proteins.