Development of protein mimics for intracellular delivery.
Development of protein mimics for intracellular delivery.
复制标题
DOI：
10.1002/bip.22658
复制
发表时间：
2015-07
期刊：
影响因子：
2.9
通讯作者：
Tew GN
中科院分区：
文献类型：
--
作者：
deRonde BM;Tew GN
设计用于治疗的递送剂是一个持续的挑战。随着治疗和所需货物变得更加复杂，对改进的运载工具的需求变得至关重要。优秀的运载工具必须保证货物的稳定性，保持货物的溶解性，促进高效的运送和释放。为了解决这些问题，许多研究小组从大自然中寻找设计灵感。蛋白质，如HIV-1达特和Apneapedia同源结构域蛋白，能够穿过细胞膜。然而，由于其结构的复杂性，它们在实验室环境中再现具有综合挑战性。能够结合这些蛋白质的关键特征，使细胞能够进入更简单的支架，为开发具有更好性能的新递送试剂开辟了广泛的机会。本文综述了基于细胞穿透肽的蛋白质模拟物的发展，以及这些分子及其蛋白质对应物的结构-活性关系如何最终导致聚合物支架的使用。这些支架偏离了正常的肽骨架，允许更简单的合成程序来制造载体并调整化学组成以满足特定应用的需求。聚合蛋白模拟物的成功设计将使研究人员能够进一步了解有效递送所需的蛋白质和肽的关键特征，并设计下一代更有效的递送试剂。
Designing delivery agents for therapeutics is an ongoing challenge. As treatments and desired cargoes become more complex, the need for improved delivery vehicles becomes critical. Excellent delivery vehicles must ensure the stability of the cargo, maintain the cargo’s solubility, and promote efficient delivery and release. In order to address these issues, many research groups have looked to nature for design inspiration. Proteins, such as HIV-1 TAT and Antennapedia homeodomain protein, are capable of crossing cellular membranes. However, due to the complexities of their structures, they are synthetically challenging to reproduce in the laboratory setting. Being able to incorporate the key features of these proteins that enable cell entry into simpler scaffolds opens up a wide range of opportunities for the development of new delivery reagents with improved performance. This review charts the development of protein mimics based on cell-penetrating peptides and how structure-activity relationships with these molecules and their protein counterparts ultimately led to the use of polymeric scaffolds. These scaffolds deviate from the normal peptide backbone, allowing for simpler, synthetic procedures to make carriers and tune chemical compositions for application specific needs. Successful design of polymeric protein mimics would allow researchers to further understand the key features in proteins and peptides necessary for efficient delivery and to design the next generation of more efficient delivery reagents.