PAS蛋白融合修饰研究进展

Research Progress in Fusion Modification of PAS

PAS蛋白修饰技术是指通过基因融合的方法将具有功能性的多肽与由脯氨酸、丙氨酸和丝氨酸组成的多肽序列连接起来并通过基因工程的手段进行融合表达,实现对多肽的修饰。目前,对于小分子多肽类药物而言,其较小的体积导致在血浆中的半衰期较短,而临床上应用PEG对小分子多肽药物进行修饰,使得其具有较大的流体力学体积,增加其药理活性。但是近年来,随着越来越多的PEG修饰药物进入临床应用市场,PEG化学多聚物的安全性弊端被不断发现。因此,寻找PEG化以外的更为安全有效的方法是非常有必要的,而PAS在小分子多肽修饰方面展示出了巨大的优势。就针对于PAS蛋白修饰技术的设计思路和优势,以及在应用方面取得的最新进展进行具体的阐述。

PAS protein modification technology refers to that functional polypeptides with polypeptide sequences composed of proline,alanine and serine by gene fusion are linked and fusion expression is conducted by gene engineering,thus polypeptide modification is achieved.At present,for small molecule polypeptide drugs,its smaller volume leads to a shorter half-life in plasma,and the clinical application of PEG to modify small molecule polypeptide drugs makes it have a larger hydrodynamic volume and thus its pharmacological activity is increased.However,with more and more PEG modified drugs entering the clinical application market in recent years,the safety drawbacks of PEG chemical polymers have been constantly uncovered.Therefore,it is necessary to seek more safe and effective methods besides PEG modification,and PAS has shown great advantages in small molecular polypeptide modification.In this paper,the design ideas and advantages of PAS protein modification technology,as well as the latest progress in application are described in detail.