类弹性蛋白多肽的生物合成及其药物递送应用

杨兆颖; 张帆; 郭建文; 高卫平

doi:10.12211/2096-8280.2021-094

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类弹性蛋白多肽的生物合成及其药物递送应用

特约评述 | 更新时间：2025-03-20

- 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
- 合成生物学 2022年3卷第4期页码：728-747
- 作者机构：
  
  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
- 作者简介：
  
  [ "杨兆颖（1993—），女，博士，博士后。研究方向为生物偶联物与生物材料。E-mail：yangzhaoying18@163.com" ]
  [ "张帆（1998—），女，博士研究生。研究方向为蛋白质-高分子偶联物。E-mail：m18232657001@163.com" ]
  [ "高卫平（1975—），男，研究员，博士生导师。研究方向为生物偶联物与生物材料。E-mail：gaoweiping@hsc.pku.edu.cn" ]
- 基金信息：
  
  国家自然科学基金重大项目(81991505)
- DOI：10.12211/2096-8280.2021-094
  中图分类号： Q81
- 收稿：2021-09-27，
  
  修回：2021-11-11，
  
  纸质出版：2022-08-31
- 稿件说明：
移动端阅览
杨兆颖，张帆，郭建文，高卫平. 类弹性蛋白多肽的生物合成及其药物递送应用［J］. 合成生物学， 2022， 3（4）： 728-747

YANG Zhaoying， ZHANG Fan， GUO Jianwen， GAO Weiping. Biosynthesis of elastin-like polypeptides and their applications in drug delivery［J］. Synthetic Biology Journal， 2022， 3（4）： 728-747
杨兆颖，张帆，郭建文，高卫平. 类弹性蛋白多肽的生物合成及其药物递送应用［J］. 合成生物学， 2022， 3（4）： 728-747 DOI： 10.12211/2096-8280.2021-094.

YANG Zhaoying， ZHANG Fan， GUO Jianwen， GAO Weiping. Biosynthesis of elastin-like polypeptides and their applications in drug delivery［J］. Synthetic Biology Journal， 2022， 3（4）： 728-747 DOI： 10.12211/2096-8280.2021-094.

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。

Abstract

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 (

) and reversibly phase separate into an insoluble

coacervate phase above the

. 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

hyperthermia-targeted delivery and sustained released of the drugs

in vivo

. Challenges and problems faced in this emerging field are discussed at the end of this review.

关键词

Keywords

references

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