类弹性蛋白多肽的生物合成及其药物递送应用  

Biosynthesis of elastin-like polypeptides and their applications in drug delivery

作　　者：杨兆颖 张帆[1,2] 郭建文 高卫平 YANG Zhaoying;ZHANG Fan;GUO Jianwen;GAO Weiping(Biomedical Engineering Department,Peking University,Beijing 100191,China;Institute of Medical Technology,Peking University Health Science Center,Beijing 100191,China)

机构地区：[1]北京大学跨学部生物医学工程系,北京100191 [2]北京大学医学部医学技术研究院,北京100191

出　　处：《合成生物学》2022年第4期728-747,共20页Synthetic Biology Journal

基　　金：国家自然科学基金重大项目(81991505)。

摘　　要：类弹性蛋白多肽(elastin-like polypeptide,ELP)是一种衍生于天然弹性蛋白,可人工合成的多肽聚合物。ELP具有特殊的温度响应性,它会随温度的变化表现出可逆相转变行为,并且当它与其他小分子或多肽偶联时,该温敏特性可以被充分保留。借助基因工程可以人工合成ELP与ELP融合蛋白,精确调控ELP的结构与功能,在其序列中添加反应性氨基酸或多肽。同时,ELP由天然氨基酸组成,其生物相容性好,易于生物降解,免疫原性低,无毒性作用。基于以上优势,ELP已被广泛应用于蛋白的表达纯化、体外诊断、药物递送和组织工程等生物医药领域。本文结合国内外研究报道,简要介绍了ELP的设计原理、理化特性和生物合成方法,并列举了一些ELP应用于药物递送系统中有代表性的工作,最后总结了该研究领域面临的挑战和问题。Elastin-like polypeptides(ELPs) are artificially synthetic peptide polymers inspired by human elastin.ELPs are composed of repeat units of a Val-Pro-Gly-X-Gly, where X can be any amino acid except proline, and they can exhibit different biological functions along with X residue changes. ELPs are thermally responsive and demonstrate lower critical solution temperature phase behavior. They are soluble at temperatures below a characteristic transition temperature(Tt) and reversibly phase separate into an insoluble, coacervate phase above the Tt. Moreover, the phase behavior is retained when the ELP is either genetically fused to peptides or covalently conjugated to small molecules,and this phase behavior can be adjusted through changing X residue and chain length of ELPs. As ELPs are typically produced from synthetic genes, the structure and function of ELPs can be accurately regulated through genetic engineering. The amino acids or peptides with reactive side chains can be incorporated into ELPs through recombination synthesis as well. This precision control over ELP is unmatched by synthetic polymers. Based on these properties, ELPs can be engineered to assemble into unique architecture and used as soluble macromolecular carriers,therapeutic drug depots, hyperthermia-targeted drug carriers and self-assembled micelles. Lastly, as ELPs are derived from natural protein sequences, they show desirable biological properties including excellent biocompatibility, low immunogenicity, and non-toxic effects. Due to these attributes, ELPs have been widely used in biomedical fields including protein expression and purification, in vitro diagnosis, drug delivery and tissue engineering. By focusing primarily on applications of ELPs in drug delivery, this review introduces the design principles, physicochemical properties, biosynthetic methods of ELPs and ELP conjugates, as well as exemplifies representative applications of ELPs in drug delivery, as extending the half-life of drugs, tumor targeted delivery, local delivery, hypert

关 键 词：类弹性蛋白 融合蛋白 相转变 生物材料 药物递送 

分 类 号：Q81[生物学—生物工程]